1.Effect of Dahuang Xiezhuo Prescription on Inflammation and SOCS3/TLR4 Pathway in Rats with Chronic Renal Failure
Xin XIN ; Zhenhua WU ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Qian ZHANG ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):95-104
ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription (DHXZ) on inflammation and suppressor of cytokine signaling 3 (SOCS3)/Toll-like receptor 4 (TLR4) pathway in rats with chronic renal failure (CRF), and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats, 15 were randomly selected as sham group, and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling, the rats were randomly divided into model group, DHXZ low-, medium-, high-dose groups (6.825, 13.65, 27.3 g·kg-1) and Niaoduqing Granules group (2.6 g·kg-1). The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration, hematoxylin-eosin (HE) staining and Masson staining were used to observe the morphological changes of rat renal tissue, and blood creatinine (SCr), blood urea nitrogen (BUN) and blood uric acid (UA) were tested. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expressions of SOCS3, TLR4, nuclear transcription factor (NF-κB) and myeloid differentiation factor (MyD88) were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB, MyD88, NOD-like receptor protein 3 (NLRP3) and melanoma deficiency factor 2 (AIM2). ResultCompared with the sham group, the model group had a significant inflammatory response in renal tissue, and an increase in blood SCr, BUN, UTP, IL-6, TNF-α and CRP (P<0.05). The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4, NF-κB, MyD88, NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group (P<0.05). Compared with the model group, DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr, BUN, UTP, IL-6, TNF-α and CRP (P<0.05). Additionally, DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4, NF-κB, MyD88, NLRP3 and AIM2 and the mRNA expression of TLR4 (P<0.05). ConclusionDHXZ can reduce the release and expression of inflammatory factors, inhibit the inflammatory response and improve renal function, and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.
2.Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway
Yao ZHANG ; Fei GAO ; Miao TAN ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Guodong YUAN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):203-213
ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK), silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), autophagy and apoptosis in kidney tissue of rats with membranous nephropathy (MN), and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group, model group, benazepril hydrochloride group (10 mg·kg-1), and salvianolate low-, medium-, and high-dose groups (16.7, 33.3 and 66.7 mg·kg-1). The rats were modeled by injection of cationized bovine serum albumin (C-BSA) into the tail vein. After successful modeling, rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks, and then 24-hour urine, serum and kidney tissue were collected for the detection of 24-hour urinary protein (UTP), blood urea nitrogen (BUN), serum creatinine (SCr), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The pathological changes of kidneys were observed by light microscope, electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK (p-AMPK), AMPK, phospho-SIRT1 (p-SIRT1), SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, ubiquitin-binding protein (p62), B cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), and cysteine aspartic protease-7 (Caspase-7) in rat kidney tissue were determined by immunohistochemistry (IHC). ResultCompared with the conditions in the normal group, the levels of UTP, IL-6, TNF-α, CRP and MDA in the model group were increased (P<0.05) while the levels of SOD and GSH-Px were decreased (P<0.05), and there was no difference in BUN and SCr. Compared with the model group, the administration groups had lowered UTP, IL-6, TNF-α, CRP and MDA (P<0.05) while elevated SOD and GSH-Px (P<0.05). It could be seen from hematoxylin and eosin (HE) staining, Masson staining, immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant, but after treatment with benazepril hydrochloride and salvianolate, the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group (P<0.05) while the expressions of Bax, Caspase-7 and p62 were higher (P<0.05). Compared with the model group, benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in the kidney (P<0.05) while a down-regulation in the expressions of Bax, Caspase-7 and p62 (P<0.05). ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway, the up-regulation of autophagy and the reduction of apoptosis.
3.Effect of Dahuang Xiezhuo Prescription on Renal Interstitial Fibrosis of Rats with 5/6 Nephrectomy by Regulating ROS/TXNIP/NLRP3 Pathway
Wenxuan CAO ; Xin XIN ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):81-89
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the changes in renal pathology and reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway expression in the kidney tissues of rats with 5/6 nephrectomy, and to explore the mechanism of Dahuang Xiezhuo prescription in protecting renal function and delaying renal interstitial fibrosis and the possibility. MethodNinety healthy male SD rats were randomly divided into a sham operation group, a model group, low, medium, and high-dose (6.825, 13.65, 27.30 g·kg-1) Dahuang Xiezhuo prescription groups, and a Niaoduqing granule group (2.60 g·kg-1). Except the sham operation group, 5/6 nephrectomy was used to replicate the rat model of chronic renal failure (CRF). After modeling, each administration group was given the corresponding dose of drug suspension by intragastric administration, once a day for consecutive 8 weeks. After administration, serum creatinine (SCr) and urea nitrogen (BUN) levels and 24 h urinary protein quantification (UTP) levels were detected. Western blot assay was used to detect the protein expressions of thioredoxin (TRX), TXNIP, and NLRP3. The protein expressions of TRX, TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), transformation growth factor-β (TGF-β), Collagen Ⅳ, α-smooth muscle actin (α-SMA), and fibronectin (FN) were detected by immunohistochemistry. ResultAs compared with the sham operation group, serum levels of SCr, BUN, and UTP in the model group were increased (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN proteins were increased (P<0.01), and renal interstitial fibrosis significantly occurred. As compared with the model group, the levels of SCr, 24 h BUN, and UTP in the low, medium, and high-dose Dahuang Xiezhuo prescription groups and the Niaoduqing granule group were decreased to varying degrees (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN were decreased (P<0.01), and renal interstitial fibrosis was improved to varying degrees. ConclusionDahuang Xiezhuo prescription can protect renal function and delay renal interstitial fibrosis in rats with CRF.
4.Correlation between hyponatremia and the severity of coronavirus disease 2019
Weidai ZHANG ; Senrong LU ; Mianfeng ZHANG ; Hongbin ZHENG ; Yuhan HUANG ; Suzhi CHEN ; Huizhong KANG ; Suwu WU
Chinese Critical Care Medicine 2020;32(7):774-778
Objective:To investigate the correlation between hyponatremia and the severity of coronavirus disease 2019 (COVID-19).Methods:Clinical data of 12 patients with COVID-19 admitted to Shantou Central Hospital from January 23 to February 5 in 2020 were retrospectively analyzed, including gender, age, symptoms, lab test and clinical outcomes, to analyze the change trend of blood Na + level in the patients with COVID-19. Results:Among the 12 patients with COVID-19, there were 8 males and 4 females with the mean age of (38.0±16.3) years old, most of them were admitted to the hospital with cough and/or fever. All patients had a positive nucleic acid test for 2019 novel coronavirus (2019-nCoV), and were discharged after clinical treatment with oxygen therapy, antiviral, antibacterial, anti-inflammatory, and nutritional support. All patients were of ordinary type when they were admitted to the hospital. Among them, 1 patient turned into a severe case during the course of the disease, and 1 patient showed a tendency to become severe case. It was found that 10 patients without severe conversion had an average blood Na + of (138.3±1.3) mmol/L at admission, and the lowest blood Na + during the course of disease was (135.9±3.1) mmol/L. However, 2 patients who became severe and had a tendency to become severe disease (Na + levels at admission were 140.0 mmol/L and 138.0 mmol/L, respectively) experienced hyponatremia during the course of the disease (the lowest blood Na + levels were 129.0 mmol/L and 122.0 mmol/L). Further analysis showed that the lower serum Na + level, the higher level of white blood cell count (WBC) and C-reactive protein (CRP), but serum Na + level was consistent with the change trend of lymphocytes, suggesting that hyponatremia was closely correlated with severe inflammation reaction. Conclusions:Serum Na + showed decreasing tendency during the development of COVID-19, and hyponatremia was closely related to the severity of COVID-19. It was necessary to pay great attention to the change trend of blood Na + level. However, further research was needed to obtain more reliable conclusions and explorer the pathophysiological mechanisms.
5. Effect of salvianolate on podocyte of membranous nephropathy rats induced by cationic bovine serum albumin
Chinese Traditional and Herbal Drugs 2018;49(8):1877-1883
Objective To observe the effects of salvianolate on blood biochemical indexes, pathological changes of renal tissue and expression of CD2AP and Desmin protein in membranous nephropathy rats induced by cationic bovine serum albumin. And to explore the renal protective effect of salvianolate on membranous nephropathy rats and its possible mechanism. Methods Healthy male SD rats were randomly divided into normal group and modle group. Rat models of membranous nephropathy were reproduced by injection of cationized bovine serum albumin through tail vein. Model successful rats were randomly divided into model group, benazepril group, and salvianolate groups (16.7, 33.3, and 66.7 mg/kg). Each group was given the dose of the corresponding drugs. After treatment, the level of 24 h urine total protein (UTP), serum total cholesterol (TC), triglyceride (TG), total protein (TP), albumin (ALB), urea nitrogen (BUN), and serum creatinine (Scr) were detected. Immunofluorescence, light microscope, and electron microscope were used to observe the pathological changes of rat kidney. Immunohistochemistry and real-time PCR were used to detect the expression of CD2AP and Desmin. Results Compared with the control group, levels of UTP, TC, and TG increased significantly (P < 0.01), levels of serum TP and ALB decreased significantly (P < 0.01) in the model group. Compared with the model group, the UTP, TC, and TG of each treatment group were significantly decreased (P < 0.05, 0.01), while the TP and ALB were significantly increased (P < 0.01). There was no significant difference in the UTP, TC, TG, TP, and ALB among each dosage of salvianolate and benazepril group. And there was no significant difference among each dose group of salvianolate. There was no significant difference among each groups in the level of BUN and Scr. Compared with the normal group, the expression of CD2AP in model group was significantly decreased and Desmin was significantly increased (P < 0.01). Compared with the model group, the expression of CD2AP increased and Desmin decreased in each treatment group (P < 0.01), but there was no difference among the treatment groups. Conclusion Salvianolate has kidney protective effect on membranous nephropathy rats. The mechanism may be related to up-regulating the expression of CD2AP, down-regulating the expression of Desmin, inhibiting podocyte injury and protecting the integrity of the glomerular filtration barrier.
6.Clinical reaserch of hyperbaric oxygenation combined with doxazosin in the treatment of Ⅲ type prostatitis in plateau
Xin LI ; Shaoyong LI ; Liang WANG ; Zhipeng CHEN ; Hanbin LIU ; Suzhi LI
Chongqing Medicine 2014;(6):653-655
Objective To investigate the effect of treatment and mechanism with hyperbaric oxygenation and doxazosin in pa-tients with Ⅲ type prostatitis in plateau .Methods A total of 94 patients with Ⅲ type prostatitis were divided randomizedly into hyperbaric oxygenation group (n=28) ,doxazosin treated group (n=31) and hyperbaric oxygenation and doxazosin combining trea-ted group (n= 35) .And then they were evaluated in 8 weeks treatment respectvely by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and adverse events .Prostate fluid and semen routine were examed .Results All three groups got the improved CPSI after treatment ,oxygenation-doxazosin combining treated group(82 .9% )was better than that of oxy-genation and doxazosin treated group(73 .7% and 70 .0% )(P<0 .05) .Results of prostate fluid and semen routine examination of combining treated group were significantly improved than before (P<0 .05) .No complications occurred .Conclusion Combination of hyperbaric oxygenation and doxazosin is a safe and effective therapy in the treatment of Ⅲ type prostatitis in plateau .
7.The renal boipsy data analysis of 107 patients at high altitude area in Tibet
Yan ZHOU ; Chuan LI ; Yunbing GONG ; Zhiguo MAO ; Jun WU ; Hongzhang CHEN ; Suzhi LI ; Zheng TANG ; Zhihong LIU ; Yongming DENG
Journal of Medical Postgraduates 2014;(11):1188-1190
[Abstract ] Objective Chronic renal disease,a common and frequent disease,is the most cause inducing chronic renal failure. There is an important guiding significance for renal biopsy in the diagnosis,treatment and prognosis of renal disease.The aim of this study was to analyze the characteristics of renal biopsy and the relation between pathological types and clinical presentation in Tibet. Methods Between June 2011 and December 2013 in General Hospital of Tibetan Military Command, Lhasa, percutaneous renal biopsy were per-formed in 107 renal patients.In this study, the gender, age, pathologic entities, and clinical manifestation were analyzed retrospectively. The final diagnosis was made by the clinical manifestation, laboratory examination,and pathologic results. Results The mean age at renal biopsy was 29.8 ±12.2(10~66)years in 47 male cases (43.9%) and 69 female cases (56.1%).This includes 75 Tibetan cases (70.1%), 31 Han cases (28.9%), and Bai cases (1.0%).The primary glomerular disease was 95.3%and the secondary glomerular disease was 4.7%in the total 107 cases.Fourty-four point three percent of the primary glomerular disease were male cases and 100%of secondary glomerular disease were female cases.The main pathological type of the primary glomerular disease was podocyte nephropathy (43.9%), followed by membranous nephropathy (18.7%), IgA nephropathy (11.2%), focal segmental glomerulosclerosis (9.3%) and mesangiocapillary glomerulonephritis (5.6%).The clinical manifestations of 107 cases were classified as syndrome of nephrotic syn-dromn(69.1%),urinary abnormalities(14.9%),isolated macrographic haematuria (3.7%),chronic renal failure(2.8%).Among the nephrotic syndrome,podocyte disease was 63.5%,membranous glomerulopathy was 18.9%,focal segmental glomeruolsclerosis was 8.1%,and membranoproliferative glomerulonephritis was 5.4%. Conclusion The primary glomerulonephritis was the most common glomerular diseases at high altitude area in Tibet.The most frequent type of pri-mary glomerular nephritis was podocyte disease, and the most frequent type of secondary glomerular nephritis was Henoch-Schonlein purpura glomerulonephritis.
8.Application of high volume continuous blood purification in the treatment of multiple organ dysfunction syndrome
Qichun ZHANG ; Xibin FANG ; Zhiye LI ; Weihong CHEN ; Xiaobin NI ; Suzhi CHEN ; Yang LUO ; Jiping CHEN
Chinese Journal of Primary Medicine and Pharmacy 2012;19(17):2598-2599
Objective To compare the effect of high volume continuous blood purification (CBP) with routine CBP on multiple organ dysfunction syndrome(MODS).Methods 38 patients with MODS were randomly divided into high volume CBP group( treatment group,18 cases) and routine CBP group (control group,20 cases).And they were respectively detected on mean arterial pressure(MAP),dosage of Dopamine,PaO2/FiO2,APACHE [ score,lactic acid,length of stay and mortality in ICU post-treatment 24h and 48h.Results Compared with control group,MAP and PaO2/FiO2 on treatment group were more higher( P < 0.05 ),while dosage of Dopamine,APACHE Ⅱ score,lactic acid were significantly shorter than these of treatment group( P < 0.05 ),and length of stay and mortality in ICU were significantly lower than those of treatmen group [ ( 8.54 ± 4.15 ) d vs ( 11.82 ± 5.76) d,P < 0.05:22.2% vs 35.0%,P <0.05 ].Conclusion High volume CBP could reduce the mortality in ICU compared with control group routine CBP.
9.Research on relationship between tissue quantitative distribution of 3H-Achyranthes bidentata ecdysterone and channel-tropism of herbal drugs in mice.
Mishan WU ; Suzhi ZHAO ; Lizhong REN ; Ru WANG ; Xia BAI ; Hongwei HAN ; Bin LI ; Huayue CHEN
China Journal of Chinese Materia Medica 2011;36(21):3018-3022
OBJECTIVETo study the relationship between tissue quantitative distribution and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and the channel-tropism of herbal drugs in mice.
METHOD3H-achyranthes bidentata ecdysterone was used as a tracer agent and injected into mice by the caudal vein. In 36 hours, the contents of the tracer agent of samples involving 9 different tracing phases and organ or tissue were determined in order to observe the dynamic quantitative distribution and excretion and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and to understand the channel-tropism of herbal drugs achyranthes bidentata.
RESULT3H-achyranthes bidentata ecdysterone of same organs in different tracing phases and the contents of 3H-achyranthes bidentata ecdysterone in same tracing phases of different organs were significantly different (P<0.01). 3H-achyranthes bidentata ecdysterone was mainly distributed, in the liver, kidney, adrenal gland, small intestine and lung. The concentration-time profiles of achyranthes bidentata ecdysterone in rats injected into mice by the caudal vein were shown to fit a two-compartment open model with half-lives of (778.65 +/- 12.36) min, the elimination of achyranthes bidentata ecdysterone from plasma was found to be in accord with linear kinetics.
CONCLUSIONThe above mentioned selective distribution of 3H-achyranthes bidentata ecdysterone basically coincides with the meridian affinity and zang fu selection of the traditional Chinese medicine drug Achyranthes bidentata. This study will provide a scientific basis for the channel-tropism of A. bidentata.
Achyranthes ; chemistry ; Animals ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Ecdysterone ; metabolism ; pharmacokinetics ; Isotope Labeling ; Male ; Meridians ; Mice ; Organ Specificity ; Tissue Distribution ; Tritium ; chemistry
10.Bacterial Infection after Gunshot Injury in Chongqing and Lasa:A Comparative Study
Daiping HE ; Suzhi LI ; Zuoming YIN ; Na YANG ; Shixun CHEN
Chinese Journal of Nosocomiology 2006;0(02):-
OBJECTIVE To observe Staphylococcus aureus(SAU) infection at high altitude and plain after gunshot injury. METHODS Used 7.62mm bullets to injure posterior limbs of piglets with the same age.We got contusing tissues in different time after injury,to make bacteriologic examination,identify and make a statistic analysis of SAU. RESULTS The main infection was caused by SAU after gunshot injury in two regions.From contusing tissues in two regions,the rate of contamination caused by SAU in Chongqing and Lasa was 48% and 18%,respectively.The time of SAU colonization was 3 hours at high altitude,and less 3 hours at plain.The velocity of reproduction of SAU at high altitude for 12 hours was 5-6 passages,and at plain was 4-6 passages for 3-6h.The time of remaining relative steady state between tissues and germs was 48 hours at high aititude and 24 hours at plain.The difference of the number of SAU between two regions after injury 3-36 hours was significant,But after 36 hours the difference was unsignificant. CONCLUSIONS At high altitude region,SAU is the main germ that causes contamination after gunshot injury,the velocity of reproduction of SAU is slower than that at plain,the time of infection is delayed obviously.

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