1.Clinicopathological Analysis of 11 Cases of SMARCA4(BRG1)-deficient Carcinoma
Xiaozhen JIANG ; Fengfen GUO ; Yiyun SHENG ; Shengnan LIANG ; Hongping WAN ; Kui DENG
Cancer Research on Prevention and Treatment 2024;51(6):469-474
Objective To investigate the clinicopathological features,immunophenotype,diagnosis and treatment of SMARCA4(BRG1)-deficient carcinoma.Methods Clinical data of 11 patients with SMAR-CA4(BRG1)-deficient cancer were collected.The morphologic and immunohistochemical features of this tumour were summarized,and the relevant literature was reviewed.Results Among the 11 cases of SMARCA4(BRG1)-deficient carcinoma,eight were male and three were female,with median age of 60.Seven patients underwent radical resection,and four underwent traditional joint targeted chemotherapy and immunotherapy.Microscopically,the tumor cells were epithelioid,rhabdoid or spindle-shaped,with prominent eosinophilic nucleoli and frequent mitoses(>5/10 HPF).Multiple foci of necrosis were found in the tumor tissue,a large number of tumor emboli in the blood vessels and myxoid stromal degeneration.Among these cases,11 cases showed loss of SMARCA4(BRG1)expression,whereas the CK and Vim markers were expressed,SMARCB1(INI1)expression was retained,and p53 mutation was detected.The tumor cells showed high proliferation activity(Ki-67>60%),and synaptophsin was moderately positive.Three cases were mismatch repair deficient and respectively showed the loss of MLH1/PMS2,PMS2 and MSH6 expression.Conclusion The incidence of SMARCA4(BRG1)-dificient carcinoma is low.It can be easily confused with other tumors and is difficult to be diagnosed before operation,which requires confirmation by immunohistochemistry.
2.Safety and efficacy of domestically produced novel bioabsorbable vascular scaff old in the treatment of complex coronary artery lesions for 3 years
Deng-Shuang ZHOU ; Qiong YOU ; Hai-Liang MO ; Zi-Jun WU ; Yu-Biao LIN ; Lu-Jun CHEN ; Jun-Yu FAN ; Yong-Jian LIN ; Rui-Sheng ZHANG ; Pei-Shan WAN ; Wei-Guo ZHOU ; Keng WU
Chinese Journal of Interventional Cardiology 2024;32(9):509-515
Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P<0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P>0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95%CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.
3.Single posterior osteotomy for the treatment of rigid cervical spine deformities
Xiaoyu CAI ; Tao XU ; Maimaiti MAIERDAN· ; Rui CAO ; Chuanhui XUN ; Weidong LIANG ; Jian ZHANG ; Qiang DENG ; Maimaiti PULATI· ; Jun SHENG ; Ting WANG ; Weibin SHENG
Chinese Journal of Orthopaedics 2024;44(19):1265-1272
Objective:To evaluate the safety and effectiveness of single posterior osteotomy in the correction of rigid cervical spine deformities (CSD) and to explore the indications and key surgical techniques involved.Methods:A retrospective analysis was conducted on the clinical data of 9 patients with rigid CSD who underwent single posterior osteotomy correction between June 2012 and June 2023 in the Department of Spine Surgery at the First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 4 males and 5 females, with a mean age of 19.8±27.2 years (range, 7-48 years). Among these, 5 cases were congenital CSD, 3 were post-tuberculosis deformities, and 1 was iatrogenic. Various coronal and sagittal alignment parameters were measured, including C 1, 2 angle, cervical lordosis (CL), structural scoliosis angle (SSA), structural kyphosis angle (SKA), head tilt (HT), C 2-C 7 sagittal vertical axis (CSVA), sagittal vertical axis (SVA), coronal balance distance (CBD), T 1 slope (T 1S), and the difference between T 1 tilt and cervical lordosis (T 1S-CL). Clinical outcomes were assessed using the neck disability index (NDI), visual analogue scale (VAS), and Scoliosis Research Society-22 questionnaire (SRS-22). Results:The average operation time was 273.9±76.1 min, with an average blood loss of 472.2±128.8 ml. All 9 patients were followed up for an average of 45.2±41.8 months (range, 12-116 months). A total of 7 patients underwent single-segment osteotomies (C 3, C 6 and C 7: 1 case each; C 5: 4 cases), and 2 patients underwent double-segment osteotomies (C 2 and C 7, C 3 and C 4). Four cases involved pedicle subtraction osteotomy (PSO), while 7 cases required vertebral column resection. The upper instrumented vertebra (UIV) was located at the occiput in 1 case and in the cervical spine in 8 cases. The lower instrumented vertebra (LIV) was located in the upper thoracic spine in 6 cases and in the cervical spine in 3 cases, with 2 of the latter cases having both UIV and LIV in the cervical spine. The average number of fused segments was 7.6±4.4 segments (range, 2-12 segments). All patients achieved successful bone fusion within an average of 8.8±3.2 months (range, 6-12 months). Preoperatively, the mean values for CL, SSA, SKA, HT, and CBD were 19.8° (17.2°, 30.5°), 27.4°(23.3°, 30.4°), 28.4°(25.6°, 30.1°), 9.0°(6.2°, 12.3°), and 18.5(12.3, 23.6) mm, respectively. Postoperative improvements were noted with values of -11.1°(-8.8°, -14.4°), 1.3°(0.8°, 1.6°), -11.1°(-8.6°, -14.5°), 1.6°(0.5°, 2.2°), and 9.4 (4.8-13.5) mm, respectively. At the final follow-up, these parameters were maintained, with values of -11.0°(-8.8°, -14.3°), 1.2°(0.8°, 1.5°), -11.0° (-8.6°, -14.3°), 1.5°(0.5°, 2.2°), and 9.4(4.8, 13.4) mm, respectively. Statistically significant improvements were observed between preoperative and postoperative measurements ( P<0.05), except for C 1, 2 angle, CSVA, SVA, T 1S, and T 1S-CL ( P>0.05). NDI and SRS-22 scores showed significant improvements postoperatively ( P<0.05), while VAS scores did not show a significant change ( P>0.05). Postoperative complications included transient nerve injury in two patients, one case of right central retinal artery occlusion, and one case of vertebral artery injury. Conclusion:This study confirms the safety and efficacy of single posterior osteotomy for treating rigid CSD of various etiologies. Standard PSO or modified techniques are effective for correcting cervical kyphosis, while hemivertebra resection and concave-side distraction are recommended for congenital scoliosis or kyphoscoliosis.
4.Evaluation of inhibitory effect of tumor vaccine in colon carcinoma model mice
Lu HAN ; LIANG Zhao yuan ; SHI Si wei ; YANG Li qun ; DENG Xiong wei ; SHENG Wang
Chinese Journal of Biologicals 2023;36(1):11-15+20
Objective:
To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice.
Methods:
Mouse bone marrow⁃derived dendritic cells(BMDCs)were stimulated by using CpG β⁃glucan nanoparticles(CNP)in vitro. The
BMDCs were divided into PBS group,NP group(without CpG nanoparticles),Lysate group(MC38 cell lysate)and CpG
group(CpG1826),which were determined for the expression of marker molecules on the surface by flow cytometry and for the
contents of interleukin⁃6(IL⁃6)and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃
pared by mixing 50 mg/mL tumor lysate(MC38 cell lysate)with 200 mg/mL CNP in a volume ratio of 1∶1,with which
mice were subcutaneously immunized as Vaccine group. Vaccine group,PBS group,CNP group and Lysate group were im⁃
munized once a week,for three times in total. Mice were subcutaneously inoculated with MC38 cells,2 × 105 cells for each,
in the right lower limb 1 h after the last immunization,and measured for tumor volume once every three days to plot the
tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the
levels of tumor necrosis factor⁃α(TNF⁃α)and interferon γ(IFNγ)in the blood and spleen of mice were determined by
ELISA.
Results:
CNP effectively increased the expression of CD11c+ CD80+,CD11c+ CD86+,CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro,which were significantly higher than those in other 4 groups(t = 4. 3 ~
46. 2,each P < 0. 05). Compared with that of the other three groups,the tumor volume of mice in Vaccine group decreased
significantly(t =2.6~3.4,eachP <0. 05);TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios(t =
0.5~ 1. 9,each P > 0. 05);The content of IFNγ in blood increased significantly(t = 3. 8 ~ 4. 6,P < 0. 05),while thatof
TNF⁃α showed no significant difference(t = 0. 4 ~ 2. 0,each P > 0. 05);However,the contents of IFN γ and TNF⁃α in
spleen increased significantly(t = 6. 3 ~ 13. 0,each P < 0. 001).
Conclusion
The prepared nano⁃vaccine of tumor lysate
improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.
5.Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.
Zhao-Xia DUAN ; Guan-Hua LI ; Jie-Yuan ZHANG ; Meng-Sheng DENG ; Kui-Jun CHEN ; Liang-Chao ZHANG ; Xiang-Yun CHENG ; Jing CHEN ; Guang-Ming YANG ; Jian-Min WANG
Chinese Journal of Traumatology 2023;26(3):139-146
PURPOSE:
High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances.
METHODS:
Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA).
RESULTS:
In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results.
CONCLUSION
The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals
;
Lung Injury/etiology*
;
Blast Injuries
;
Goats
;
Explosions
;
Lung/pathology*
6.Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.
Yu-Jie WU ; Bo DENG ; Si-Bo WANG ; Rui QIAO ; Xi-Wen ZHANG ; Yuan LU ; Li WANG ; Shun-Zhong GU ; Yu-Qing ZHANG ; Kai-Qiao LI ; Zong-Liang YU ; Li-Xing WU ; Sheng-Biao ZHAO ; Shuang-Lin ZHOU ; Yang YANG ; Lian-Sheng WANG
Chinese journal of integrative medicine 2023;29(12):1059-1065
BACKGROUND:
Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.
OBJECTIVE:
This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.
METHODS:
This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.
DISCUSSION
This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans
;
ST Elevation Myocardial Infarction/therapy*
;
Stroke Volume
;
Ventricular Remodeling
;
Prospective Studies
;
Microcirculation
;
Ventricular Function, Left
;
Myocardial Infarction/etiology*
;
Treatment Outcome
;
Percutaneous Coronary Intervention/adverse effects*
;
Heart Failure/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Randomized Controlled Trials as Topic
;
Multicenter Studies as Topic
7.Long-term outcomes of posterior release and reduction for irreducible atlantoaxial dislocation
Shutao GAO ; Tao XU ; Maimaiti MAIERDAN· ; Hailong GUO ; Maimaiti PULATI· ; Jun SHENG ; Qiang DENG ; Chuanhui XUN ; Weidong LIANG ; Jian ZHANG ; Rui CAO ; Abulizi YAKEFU· ; Zhouliang REN ; Ting WANG ; Weibin SHENG
Chinese Journal of Orthopaedics 2022;42(7):455-462
Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.
8.Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61.
Wan-Jun GUO ; Yi WANG ; Yu DENG ; Lin-Yan CHENG ; Xin LIU ; Ruo-Fan XI ; Sheng-Jie ZHU ; Xin-Yi FENG ; Liang HUA ; Kan ZE ; Jian-Yong ZHU ; Dong-Jie GUO ; Fu-Lun LI
Journal of Integrative Medicine 2022;20(4):376-384
OBJECTIVE:
Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.
METHODS:
The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.
RESULTS:
Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.
CONCLUSION
The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals
;
China
;
Cysteine-Rich Protein 61/metabolism*
;
Disease Models, Animal
;
Drugs, Chinese Herbal/therapeutic use*
;
Imiquimod/adverse effects*
;
Inflammation/drug therapy*
;
Intercellular Adhesion Molecule-1/genetics*
;
Interferon-gamma
;
Mice
;
Mice, Inbred BALB C
;
Psoriasis/pathology*
;
RNA, Messenger/therapeutic use*
9.Danggui Buxuetang Alleviates Oxidative Stress and Inflammation in Diabetic Kidney Disease Rats by Improving Mitochondrial Dysfunction of Podocytes
He-chao JIN ; Jia-wei QIANG ; Guan-wen ZHANG ; Sheng-ran LIANG ; Deng-zhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(3):31-40
ObjectiveTo investigate the intervention effect of Danggui Buxuetang on oxidative stress and inflammatory response in diabetic kidney disease (DKD) rats from its improvement of podocyte mitochondrial dysfunction. MethodSD rats were randomly divided into the control group and modeling group, and the ones in the latter group rats were fed a high-glucose and high-fat diet and then intraperitoneally injected with a small dose of streptozotocin (STZ) for inducing type 2 diabetes. The successfully modeled rats were randomized into the model group, high- and low-dose (1.44 and 0.72 g·kg-1) Danggui Buxuetang groups, and irbesartan (0.017 g·kg-1)group and gavaged with the corresponding drugs, while those in the normal and model groups with an equal volume of normal saline. After 20 weeks of drug intervention, the urinary microalbumin-to-urine creatinine ratio (UACR) and serum malondialdehyde (MDA) content and manganese superoxide dismutase (MnSOD) activity in each group were measured. The pathological changes in renal tissue were observed by Masson trichrome staining, and periodic acid-silver metheramine (PASM) staining, followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope (TEM). The expression level of reactive oxygen species (ROS) in rat kidney tissue was detected using a fluorescent probe dihydroethidium (DHE). The protein expression levels of peroxisome proliferator-activated receptor γ -coactivator -1α (PGC-1α), nucleotide-binding domain like receptor protein 3 (NLRP3), and Wilms tumor protein-1 (WT-1) were measured by immunohistochemistry (IHC), and the expression levels of NLRP3, interleukin-1β (IL-1β),and WT-1 in podocytes by immunofluorescence (IF) assay. The mRNA expression levels of PGC-1α and NLRP3 in the renal tissues were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expression levels of PGC-1α, MnSOD, NLRP3, and IL-1β were assayed by Western blot. ResultCompared with the normal group, the model group exhibited elevated UACR and MDA content, weakened MnSOD activity (P<0.01), glomerular hypertrophy, thickened basement membrane, mesangial hyperplasia, increased extracellular matrix, K-W nodules, podocyte mitochondrial swelling, disordered mitochondrial cristae, foot process fusion or loss, vacuolization, increased ROS (P<0.01), enhanced NLRP3 and IL-1β but diminished WT-1 expression in podocytes, down-regulated PGC-1α mRNA expression (P<0.01) and PGC-1α and MnSOD protein expression (P<0.01), and up-regulated NLRP3 mRNA expression and NLRP3 and IL-1β protein expression (P<0.01). Compared with the model group, Danggui Buxuetang high-dose group significantly decreased UACR and MDA, enhanced MnSOD activity (P<0.05, P<0.01), improved renal histopathology and podocyte mitochondrial ultrastructure, decreased ROS (P<0.05, P<0.01) and NLRP3 and IL-1β expression in podocytes, enhanced WT-1 expression in podocytes, up-regulated the mRNA and protein levels of PGC-1α and MnSOD, and down-regulated the mRNA and protein levels of NLRP3 and IL-1β (P<0.05, P<0.01). ConclusionDanggui Buxuetang alleviates oxidative stress, reduces inflammatory response, protects kidney, and delays the progression of DKD possibly by improving the mitochondrial dysfunction in podocytes of DKD rats.
10.Effect of Danggui Buxuetang on Podocyte Injury in Diabetic Kidney Disease Rats: An Exploration Based on RIPK1/RIPK3/MLKL Signaling Pathway
He-chao JIN ; Guan-wen ZHANG ; Sheng-ran LIANG ; Jia-wei QIANG ; Deng-zhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(3):41-48
ObjectiveTo observe the effect of Danggui Buxuetang on the podocyte injury and receptor-interacting protein kinase 1/receptor-interacting protein kinase3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) signaling pathway in diabetic kidney disease (DKD) ratsand to explore its possible mechanism against DKD. MethodEight of the 50 SD rats were randomly classified intoa normal group, and the remaining were fed a high-glucose and high-fat diet for six weeks and then intraperitoneally injected with 0.035 g·kg-1streptozotocin (STZ) for inducing type 2 diabetes. After successful modeling,they were randomized into the model group,high- and low-dose (1.44,0.72 g·kg-1) Danggui Buxuetang groups, and irbesartan (0.017 g·kg-1)group. After 20 weeks of drug intervention, the fasting blood glucose (FBG), kidney index (KI),and urinary microalbumin-to-urine creatinine ratio (UACR)were detected in each group. The pathological changes in renal tissue were observed by hematoxylin-eosin (HE) staining, followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in renal tissue of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the protein expression levels of RIPK1, RIPK3, and MLKL in rat kidney tissue by immunohistochemistry. The apoptosis rate of podocytes was detected by in situ nick end-labeling (TUNEL) assay. The mRNA expression levels of RIPK1, RIPK3, and MLKL in kidney tissue of rats were measured by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expression levels of RIPK, RIPK3, and MLKL and podocyte marker Wilms tumor protein-1 (WT-1) in rat kidney tissue were assayed by Western blot. ResultCompared with the normal group, the model group exhibited elevated FBG, UACR, and KI (P<0.01), glomerular hypertrophy, thickened basement membrane, increased extracellular matrix, mesangial hyperplasia, foot process fusion or loss, enhanced apoptosis in renal tissue, up-regulated TNF-α and IL-6 levels (P<0.01) and RIPK1/RIPK3/MLKL mRNA and protein expression (P<0.01), and down-regulated WT-1 protein expression. Compared with the model group, Danggui Buxuetang high-dose group significantly reduced the levels of FBG, UACR, and KI, improved renal histopathology, podocyte loss, and apoptosis in renal tissue, down-regulated TNF-α and IL-6 levels and RIPK1/RIPK3/MLKL mRNA and protein expression (P<0.05, P<0.01), and up-regulated WT-1 protein expression. ConclusionDanggui Buxuetang alleviates podocyte injury and delays the development of DKD possibly by regulating the RIPK1/RIPK3/MLKL signaling pathway.


Result Analysis
Print
Save
E-mail