糖肾宁对KK-Ay小鼠足细胞上皮间质转分化的作用研究  

Study on effects of Tangshenning on epithelial mesenchymal transdifferentiation of podocyte in KK-Ay mice

作　　者：崔方强 高彦彬[2] 王悦芬[1] 孟元[1] 蔡朕[1] 刘志强 江心灿 赵文景[1] CUI Fangqiang;GAO Yanbin;WANG Yuefen;MENG Yuan;CAI Zhen;LIU Zhiqiang;JIANG Xincan;ZHAO Wenjing(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院肾病科,100010 [2]首都医科大学中医药学院,中医络病研究北京市重点实验室

出　　处：《环球中医药》2020年第6期953-957,共5页Global Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金(81703989);北京市自然科学基金面上项目(7182069,7172096)。

摘　　要：目的探讨糖肾宁对KK-Ay小鼠足细胞上皮间质转分化的影响。方法采用KK-Ay小鼠建立糖尿病肾病小鼠模型,随机分为模型组、糖肾宁组及缬沙坦组,每组10只,并将10只C57BL/6J小鼠作为正常对照组。各组小鼠干预给药12周后处死,心尖取血、摘取双侧肾脏,进行相应指标检测。使用酶联免疫法检测血清肌酐及尿素氮水平,PAS染色观察各组小鼠肾组织细胞外基质增生情况,免疫组化检测各组小鼠肾组织Collagen I及FN蛋白表达,WB及RT-PCR检测各组小鼠足细胞P-cadherin和FSP-1的蛋白及mRNA表达。结果(1)与正常对照组相比,模型组小鼠血清肌酐、尿素氮水平明显升高(P<0.05);与模型组相比,糖肾宁组及缬沙坦组小鼠血清肌酐、尿素氮水平明显降低(P<0.05)。(2)与正常对照组相比,模型组小鼠肾小球细胞外基质明显增生,基质蛋白Collagen I及FN表达上调(P<0.05);与模型组相比,糖肾宁组及缬沙坦组小鼠肾小球细胞外基质增生减轻,基质蛋白Collagen I及FN表达明显下调(P<0.05)。(3)与正常对照组相比,模型组小鼠足细胞P-cadherin蛋白及mRNA表达明显下调(P<0.05),FSP-1蛋白及mRNA表达明显上调(P<0.05);与模型组相比,糖肾宁组及缬沙坦组小鼠足细胞P-cadherin蛋白及mRNA表达明显上调(P<0.05),FSP-1蛋白及mRNA表达明显下调(P<0.05)。结论糖肾宁能够抑制糖尿病肾病小鼠足细胞上皮间质转分化,可能是其减轻肾小球细胞外基质增生、延缓疾病进展的分子机制。Objective To observe the effect of Tangshenning on epithelial mesenchymal transdifferentiation of podocyte in KK-Ay mice.Methods The DN mouse model was established by KK-Ay mice.They were randomly divided into the model group,Tangshenning group and valsartan group,with 10 mice in each group,and 10 C57BL/6J mice were used as the normal group.After intervention administration for 12 weeks,mice in each group were sacrificed,then blood was taken from the apex of heart,bilateral kidneys were removed,and the corresponding indexes were detected.The levels of serum creatinine and urea nitrogen were measured by enzyme-linked immunoassay.The proliferation of extracellular matrix in renal tissues of each group mice was observed by PAS staining.The protein expression of Collagen I and FN in renal tissues of mice in each group were detected by immunohistochemical staining.The protein and mRNA expression levels of P-cadherin and FSP-1 of podocytes in each group mice were detected by western bolt and real-time quantitative PCR.Results Compared with the normal group,the levels of serum creatinine and urea nitrogen in model group increased significantly(P<0.05).Compared with the model group,the levels of serum creatinine and urea nitrogen in Tangshenning group and valsartan group decreased(P<0.05).Compared with the normal group,the glomerular extracellular matrix of the model group was significantly proliferated,and the expression of matrix protein Collagen I and FN were up-regulated(P<0.05).Compared with model group,the proliferation of extracellular matrix in the glomerular of mice in the Tangshenning group and valsartan group was reduced,and the expression levels of matrix protein Collagen I and FN were down-regulated(P<0.05).compared with normal group,the protein and mRNA expression levels of podocytes in the model group mice were down-regulated(P<0.05),the protein and mRNA expression levels of FSP-1 were up-regulated(P<0.05).Compared with model group,the protein and mRNA expression levels of P-cadherin of podocytes in Tangsh

关 键 词：糖肾宁 糖尿病肾病 细胞外基质 足细胞 上皮间质转分化 

分 类 号：R285.5[医药卫生—中药学]