保肾通络方对糖尿病肾病小鼠肾小管间质纤维化及上皮细胞间充质转分化的影响OACSTPCD
Effect of Baoshen Tongluo decoction on renal tubular interstitial fibrosis and epithelial-mesenchymal transition in DN mice
目的:观察保肾通络方对糖尿病肾病(DN)小鼠肾小管间质纤维化及上皮细胞间充质转分化(EMT)的影响.方法:选用KK-Ay小鼠作为DN模型小鼠,随机分为模型组、保肾通络方组及缬沙坦组,正常对照组小鼠选用C57 BL/6J 小鼠.保肾通络方组小鼠给予保肾通络方灌胃治疗,缬沙坦组小鼠给予缬沙坦灌胃治疗,模型组、正常对照组小鼠给予剂量相同的蒸馏水灌胃治疗;灌胃给药 12 周后检测各组血清肌酐、尿素氮水平,HE、PAS、Masson染色观察肾组织病理改变,同时进行细胞外基质蛋白Collagen Ⅰ、FN及肾小管 EMT标志蛋白α-SMA、E-cadherin表达检测.结果:模型组小鼠血清肌酐、尿素氮水平较正常对照组明显升高(均P<0.05),保肾通络方组及缬沙坦组小鼠血清肌酐、尿素氮水平较模型组明显降低(均P<0.05).与正常对照组相比,模型组小鼠肾小管出现明显的间质纤维化及上皮细胞脱落、空泡变性,而保肾通络方组及缬沙坦组小鼠上述病理改变均明显减轻.模型组小鼠肾小管Collagen Ⅰ、FN蛋白及mRNA表达较正常对照组明显上调(均P<0.05),保肾通络方组及缬沙坦组小鼠肾小管Collagen Ⅰ、FN蛋白及 mRNA表达较模型组明显下调(均P<0.05).与正常对照组相比,模型组小鼠肾小管上皮细胞α-SMA蛋白及 mRNA表达明显上调,E-cadherin蛋白及 mRNA表达明显下调(均P<0.05);与模型组相比,保肾通络方组及缬沙坦组小鼠α-SMA 蛋白及 mRNA 表达明显下调,E-cadherin蛋白及 mRNA 表达明显上调(均P<0.05).结论:保肾通络方能够改善DN小鼠肾小管间质纤维化,减轻肾小管 EMT.
Objective:To observe the effect of Baoshen Tongluo decoction on renal tubular interstitial fibrosis and epithelial-mesenchymal transition in DN mice.Methods:The model KK-Ay mice were separated into DN group,XST group and BSTL group randomly.C57 BL/6J mice performed for NC group.Mice in BSTL group were given BSTL.Mice in XST group were given XST.Mice in DN and NC group were given distilled water.All mice were suc-cessive administration for 12 weeks.Serum creatinine,urea nitrogen and 24 h urine protein was detected.Renal tubu-lar interstitial fibrosis was detected by HE,PAS and Masson staining.Immunohistochemistry and RT-PCR were used for detecting Collagen Ⅰ,FN,α-SMA and E-cadherin protein and mRNA expression.Results:Serum creatinine and urea nitrogen levels of mice in DN group were significantly higher than those in NC group(all P<0.05),while se-rum creatinine and urea nitrogen levels of mice in BSTL group and XST group were significantly lower than those in DN group(all P<0.05).Compared with NC group,the renal tubules in the DN group showed obvious interstitial fi-brosis,epithelial cell exfoliation and vacuolar degeneration,while the above pathological changes were significantly re-duced in BSTL group and XST group.The expression of Collagen Ⅰ and FN protein and mRNA in renal tubules of mice in DN group were significantly up-regulated compared with those in NC group(all P<0.05),while the expres-sion of Collagen Ⅰ and FN protein and mRNA in renal tubules of mice in BSTL group and XST group were signifi-cantly down-regulated compared with those in DN group(all P<0.05).Compared with NC group,the expression of α-SMA protein and mRNA in renal tubular epithelial cells in DN group was significantly up-regulated,and the ex-pression of E-cadherin protein and mRNA was significantly down-regulated(all P<0.05).Compared with DN group,α-SMA protein and mRNA expression in BSTL group and XST group were significantly down-regulated,while E-cadherin protein and mRNA expression were significantly up-regulated(all P<0.05).Conclusion:Baoshen Tongluo decoction can alleviate proteinuria and ameliorate renal function of DN,which partially through decreasing renal tubule interstitial fibrosis and epithelial-mesenchymal transition in DN.
崔方强;江心灿;王悦芬;孟元;蔡朕;赵文景
首都医科大学附属北京中医医院,北京 100010
临床医学
糖尿病肾病保肾通络方益肾活血通络肾小管上皮细胞间充质转分化间质纤维化
Diabetic nephropathyBaoshen Tongluo decoctionYishen Huoxue TongluoRenal tubular epithe-lial cellsEpithelial-mesenchymal transitionInterstitial fibrosis
《陕西中医》 2024 (008)
1011-1015,1025 / 6
国家自然科学基金资助项目(81703989);北京市自然科学基金资助项目(7222271);首都医科大学科研培育基金资助项目(PYZ22163)
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