ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.

ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase （JNK）/p38 mitogen-activated protein kinase （p38 MAPK） pathway. MethodsA rat ear acne model was established in SD rats， and the rats were divided into a blank group， a model group， and low-， medium-， and high-dose groups of modified Danggui Shaoyaosan （7.15， 14.30， 28.60 g·kg·d^-1）， with six rats in each group. After the administration for 14 consecutive days， morphological changes in the rats' auricles were observed， and hematoxylin-eosin （HE） staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the ear tissue. Quantitative reverse transcription polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression levels of Caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， JNK， and p38 MAPK in the ear tissue. Additionally， Western blot analysis was conducted to assess the protein levels of Caspase-3， Bcl-2， Bax， JNK， and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group， rats in the model group exhibited redness， swelling， thickening， hardening， dryness， and roughness of the auricle. The surface showed sebaceous scales and desquamation， accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization， epidermal thickening， dermal collagen fiber degeneration and necrosis， subcutaneous muscle degeneration and necrosis， inflammatory cell infiltration， and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK were significantly increased （P<0.01）， while those of Bcl-2 were significantly decreased （P<0.01）. In comparison to the model group， the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle， with varying degrees of histopathological damage reduction. Additionally， the mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK in the tissue were significantly decreased （P<0.05， P<0.01）， while those of Bcl-2 were significantly increased （P<0.05， P<0.01）. Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin， kaempferol， luteolin， quercetin， wogonin， and baicalein. These compounds exerted their effects by modulating core targets such as TNF， IL-1β， Caspase-3， and Bcl-2， thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway， thereby alleviating inflammation and apoptosis.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide （LPS）-induced acute kidney injury （AKI） rats based on the Kelch-like epichlorohydrin-related protein-1 （Keap1）/nuclear factor erythroid-2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway. MethodsSixty male SD rats were randomly divided into normal group， model group， quercetin high-dose （100 mg·kg^-1） and low-dose （10 mg·kg^-1） groups， ferroptosis inhibitor Ferrostatin 1 （FER1） group （5 mg·kg^-1）， and quercetin high-dose + Nrf2 inhibitor group （ML385， 30 mg·kg^-1）. Except for the normal group， the AKI rat model was established in each group by intraperitoneal injection of LPS （10 mg·kg^-1）. Following successful modeling， each treatment group received the corresponding dose of drug intervention， while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of Fe²⁺， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） in renal tissue were detected. Hematoxylin-eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species （ROS） levels in renal tissue were detected by immunofluorescence （IF）. The protein and mRNA expression levels of Keap1， Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， transferrin receptor （TFR1）， and kidney injury molecule-1 （KIM-1） were assessed by immunohistochemistry （IHC） and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the normal group， the model group exhibited significantly elevated serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue， and significantly reduced SOD and GSH levels （P<0.01）. Pathological injury in renal tissue was severe， with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly elevated， while those of Nrf2， HO-1， and GPX4 were significantly decreased （P<0.01）. Compared with the model group， serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction， while SOD and GSH levels were significantly increased （P<0.05）. Pathological injury in renal tissue was markedly alleviated， mitochondrial damage improved， and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly decreased， while those of Nrf2， HO-1， and GPX4 were significantly increased， with the most notable improvement in the high-dose quercetin group （P<0.05）. In comparison to the high-dose quercetin group， the ML385 group significantly weakened the protective effect of quercetin on AKI rats （P<0.05）. ConclusionQuercetin effectively inhibits ferroptosis， improves renal tissue injury， and repairs renal function in AKI rats， and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.

ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome （PCOS） by regulating the mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） pathway. MethodsAccording to the random number table method， 60 SPF female SD rats were randomized into a normal group （n=10） and a modeling group （n=50）. The normal group received routine feeding， while the modeling group was administrated with letrozole （1 mg·kg^-1·d^-1） by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model， diane-35 （0.2 g·kg^-1·d^-1）， high- （16.04 g·kg^-1·d^-1）， medium- （8.02 g·kg^-1·d^-1）， low- （4.01 g·kg^-1·d^-1） dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage， and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment， Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， testosterone （T）， and progesterone （PROG） in the plasma， as well as interleukin-1 beta （IL-1β）， tumor necrosis factor-alpha （TNF-α）， and interleukin-10 （IL-10） in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase （ERK）， c-Jun N-terminal kinase （JNK）， p38 MAPK， NF-κB p65， IκBα， p-JNK， p-ERK， p-p38 MAPK， p-NF-κB p65， and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK， JNK， p38 MAPK， NF-κB p65， and IκBα in the ovarian tissue. ResultsCompared with the normal group， the model group was in the estrus phase， with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation （P<0.05）， and lowered levels of FSH and E₂ and elevated levels of LH， T， and LH/FSH in the plasma （P<0.05）. Compared with the model group， high-， medium-， and low-dose modified Guishenwan recovered the estrous cycle， increased the generation of granulosa cells and corpus luteum， reduced the number of vesicles， elevated the levels of FSH and E₂， and lowered the levels LH， T， and LH/FSH （P<0.05， P<0.01） in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore， subsequent experiments for exploring the treatment mechanism were conducted in the normal group， model group， and high-dose modified Guishenwan group. The results showed that compared with the model group， high-dose modified Guishenwan lowered the levels of IL-1β， TNF-α， and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue （P<0.05， P<0.01）， down-regulated the protein levels of p-ERK， p-JNK， p-p38 MAPK， p-NF-κB p65， and p-IκBα， while up-regulating the protein level of IκBα （P<0.01）. At the same time， the mRNA levels of ERK， JNK， p38 MAPK， and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated （P<0.05， P<0.01）. ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects， which may be related to inhibition of the MAPK/NF-κB pathway.

ObjectiveTo investigate the therapeutic effect and mechanism of modified Chunzetang on bladder fibrosis and detrusor function in rats with neurogenic bladder urinary retention induced by spinal cord injury. MethodsIn this study， an improved Hassan Shaker spinal cord transection method was used to establish a model of neurogenic bladder urinary retention induced by spinal cord injury， and rats with a spinal cord injury behavior score of 0 were selected for follow-up experiments. The selected rats were randomly divided into a model group （normal saline gavage）， low-dose traditional Chinese medicine （TCM） group （gavage of 14.4 g·kg^-1 modified Chunzetang）， high-dose TCM group （gavage of 28.8 g·kg^-1 modified Chunzetang）， positive drug group ［intraperitoneal injection of 0.05 g·kg^-1 nuclear transcription factor-κB （NF-κB） inhibitor pyrrolidine dithiocarbamate （PDTC）］， and combination group （intraperitoneal injection of 0.05 g·kg^-1 PDTC + gavage of 28.8 g·kg^-1 modified Chunzetang）. The rats in these groups were administrated with corresponding drugs once a day for four weeks. The BL-420s biofunction acquisition system was used in the experiment to calculate the urodynamic indexes， and the isolated bladder was quickly weighed. The detrusor traction experiment was used to record the minimum bladder contraction tension and frequency in each group. The pathological morphology and tissue fibrosis of detrusor in each group observed by Hematoxycin-eosin （HE） staining and Masson staining were compared. The expression level of α-smooth muscle actin （α-SMA） was detected by immunohistochemistry. Western blot was used to detect the protein expression of NF-κB p65， nuclear transcription factor-κB suppressor protein α （IκBα）， transforming growth factor-β₁ （TGF-β₁）， type Ⅰ collagen （ColⅠ）， and type Ⅲ collagen （ColⅢ） in bladder tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of IL-6， IL-1β， and TNF-α. ResultsCompared with that in the sham operation group， the pressure at the urinary leakage point in the model group decreased （P<0.01）， and the bladder mass， bladder contractile tension， maximum bladder capacity， and bladder compliance increased （P<0.05，P<0.01）. HE staining showed that the arrangement of bladder epithelial cells was disordered， and the pathological manifestations such as mucosa and myometria neutrophil infiltration were obvious. The lamina propria structure was destroyed， and the muscle fiber arrangement was disordered. The interstitial widening and tissue edema were obvious. Masson staining showed that the bladder wall of the model group had more collagen fiber deposition， and the degree of detrusor fibrosis was more severe. The content of detrusor in the visual field was reduced. At the same time， the protein expressions of NF-κB p65， TGF-β₁， IκBα， ColⅠ， and ColⅢ in bladder tissue of rats in the model group were significantly increased （P<0.01）， and the serum levels of IL-6， IL-1β， and TNF-α were significantly increased （P<0.05）. Compared with that in the model group， the pressure at the urinary leakage point in the modified Chunzetang and positive drug groups was increased （P<0.05）， and the wet bladder weight， minimum bladder contractile tension， maximum bladder capacity， and bladder compliance were restored （P<0.05， P<0.01）. HE and Masson showed that the bladder epithelial cells were relatively neatly arranged， and the structure of the bladder lamina propria was relatively stable. The detrusor bundles were arranged in an orderly manner， and the interstitium was narrow. The degree of tissue edema was relatively low， and the degree of bladder detrusor fibrosis in the modified Chunzetang and positive drug groups was reduced， while the degree of bladder detrusor fibrosis in the positive drug group and combination groups was not obvious. The results of Western blot showed that the expression of NF-κB p65， IκBα， TGF-β₁， ColⅠ， and ColⅢ in bladder tissue， as well as the serum levels of IL-6， IL-1β， and TNF-α in modified Chunzetang and positive drug groups were significantly lower， and the expression of bladder tissue-related proteins and the serum levels of IL-6， IL-1β， and TNF-α in the TCM groups decreased significantly with the increase in dose （P<0.05）. The results of immunohistochemistry suggested that modified Chunzetang could fully affect the expression of α-SMA in bladder tissue. ConclusionModified Chunzetang can inhibit collagen deposition in bladder tissue of rats with urinary retention induced by spinal cord injury， delay the occurrence and development of bladder fibrosis， and protect the normal contractile function of bladder detrusor， and its mechanism may be related to inhibiting the NF-κB/TGF-β₁ signaling pathway， reducing the production of NF-κB p65， IκBα， TGF-β₁， ColⅠ， ColⅢ， and other related proteins， and protecting the muscle strength of detrusor.