机构地区:[1]湖南中医药大学,湖南长沙410208 [2]湖南省第二人民医院,湖南长沙410007
出 处:《中国中医药信息杂志》2020年第12期32-37,共6页Chinese Journal of Information on Traditional Chinese Medicine
基 金:国家自然科学基金(81503442、81603470);湖南省教育厅科研项目(17B197)。
摘 要:目的观察六味地黄汤对慢性肾衰竭大鼠肾组织紧密连接蛋白1(ZO-1)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)表达的影响,探讨其干预肾间质纤维化的作用机制。方法健康雄性SD大鼠随机分为假手术组、模型组、六味地黄汤组和依那普利组。5/6肾切除术复制慢性肾衰竭模型,各给药组给予相应药物灌胃,每日1次。给药8周后,腹主动脉放血法处死大鼠,检测大鼠肾功能指标,HE染色观察肾组织病理变化,Masson染色观察胶原纤维沉积,免疫组化检测肾组织ZO-1、N-cadherin、Vimentin蛋白表达。结果与假手术组比较,模型组大鼠24 h尿蛋白、血尿素氮和血肌酐水平明显升高(P<0.05);肾组织病变明显,大量胶原纤维沉积(P<0.05);肾组织ZO-1蛋白表达明显降低(P<0.05),N-cadherin、Vimentin蛋白表达明显升高(P<0.05)。与模型组比较,六味地黄汤组大鼠24h尿蛋白、血尿素氮和血肌酐水平明显降低(P<0.05);肾组织病变程度减轻,少量胶原纤维沉积(P<0.05);肾组织ZO-1蛋白表达明显升高(P<0.05),N-cadherin、Vimentin蛋白表达明显降低(P<0.05)。结论六味地黄汤通过上调ZO-1的表达,下调N-cadherin、Vimentin的表达,延缓肾间质纤维化,其作用机制与抑制肾小管上皮细胞间充质转化有关。Objective To observe the effects of Liuwei Dihuang Decoction on the expressions of ZO-1,N-cadherin and Vimentin in renal tissue of rats with chronic renal failure;To explore its mechanism in the renal interstitial fibrosis.Methods Healthy male SD rats were randomly divided into sham-operation group,model group,Liuwei Dihuang Decoction group and Enalapril group.5/6 nephrectomy was performed to replicate chronic renal failure model.Rats in each administration group were given intragastric administration once a day.8 weeks after medication,the rats were killed by abdominal aorta bleeding.Renal function was measured.Pathological changes were observed by HE staining.Collagen fiber deposition was observed by Masson staining.The expressions of ZO-1,N-cadherin,Vimentin protein were detected by immunohistochemistry.Results Compared with sham-operation group,24 h urinary protein,blood urea nitrogen and serum creatinine in model group significantly increased(P<0.05),renal tissue lesions significantly increased(P<0.05),collagen fiber deposition significantly increased(P<0.05);the protein level of ZO-1 protein in renal tissue significantly decreased(P<0.05),and the protein levels of N-cadherin and Vimentin significantly increased(P<0.05).Compared with the model group,the levels of 24 h urine protein,blood urea nitrogen and serum creatinine were significantly decreased(P<0.05)in the Liuwei Dihuang Decoction group,and the degree of renal lesion was reduced,a small amount of collagen deposition appeared(P<0.05);the protein level of ZO-1 protein increased(P<0.05),while the protein levels of N-cadherin and Vimentin decreased(P<0.05).Conclusion Liuwei Dihuang Decoction can delay renal interstitial fibrosis by up-regulating the expression of ZO-1 and down-regulating the expressions of N-cadherin and Vimentin,and the mechanism may be related to the inhibition of renal tubular epithelial-mesenchymal transformation.
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