| Objective:The purpose of this study was to investigate the effects of Liuwei Dihuang Decoct ion on HIF-1?,Twist and epithelial cadherin E(E-cadherin)signal pathway in 5/6 n ephr e c t omy rats,and to provide experimental basis for de laying the progression of renal EMT and renal fibrosis.Methods:60 SPF male rats were divided into blank control group(n=10),sham operation group(n=10)and operat ion group(n=40)according to random number table metho d.In the operation group,5/6 nephrectomy method was used to prepare renal fibrosis model.After successful mode li ng,1 dead animal in the operat ion group was remove d and randomly divided into model group(n=13),Liuwei Dihuan g Tang group(n=13)and enalapril group(n=13).The bl ank control group,sham operation group and model group w ere gavaged with distilled water,and the Liuwei Dihuang Decoction group and enalapril group were gavaged with cor responding drugs,respectively.A total of 8 weeks of trea tment.After 8 weeks,blood,urine and kidney tissues were collected to detect renal function.Pathomorphological ch ange s were observed by HE staining.Masson staining was us ed to evaluate the percentage of collagen area.HIF-1?,Tw ist and E-cadherin protein expression were detected by im munohistochemistry.The expression of HIF-1?,Twist and E-cadherin genes were detected by real-time fluorescence q uantitative PCR.Results:The body weight of blank group and sham operation group increased significantly.Compared with sham operatio n group,the body weight of rats in model group was signi f i cantly decreased(P<0.05);Compared with model group,th e weight gain of rats in Liuwe i Dihuang Decoction and ena lapril groups was significantly higher(P<0.05);24 h urin ary protein,blood urea nitrogen and serum creatinine ren al function indexes,compared with the sham operation gro up,the values of model group were significantly increase d,and the renal damage was serious(P<0.05);Compared wit h model group,Liuwei Dihuang decoct ion group was signifi cantly decreased(P<0.05).HE and Masson staining showed t hat compared with the sham operation group,the pathologi cal damage of the kidney in the model group was more s eri ous,with a large amount of collagen fiber deposition and obvious fibrosis,and the percentage of collagen area in the renal tubulointerstitium was the highest.Compared wi th the model group,pathological damage,blue collagen de position,collagen area percentage of renal tubule inter s titium and fibrosis were significantly reduced in the Liu we i Dihuang Decoction group and the enalapril group.Immun ohistochemical results and quantitative real-time PCR res ults showed that compared with sham operation group,the protein levels and mRNA expression of HIF-1? and Twist i n kidney tissue of model group were significantly increas ed(P<0.05),while the protein level and mRNA expression of E-cadher in in model group were significantly decreased(P<0.05).Compared with model group,after 8 weeks of tr e atment,the protein levels and mRNA expression levels of HIF-1? and Twist in kidney tissue of rats in Liuwei Dihu ang decoction group and enalapril group were significantl y decreased(P<0.05),while the protein level and mRNA ex pression of E-cadherin were significantly increased(P<0.05).Conclusion:Liuwei Dihuang Decoct ion can reduce the damage of renal function in 5/6 nephrectomy rats and has therapeutic effect on the pathological changes of renal structure.Liuwei Dihuang Decoction can reduce the expression of HIF-1?by improving renal hypoxia,The latter down-regulated the expression of TWIST and increased the expression of E-cadherin in epithelial cells,thereby inhibiting the occurrence of mesenchymal transdifferentiation(EMT)of renal tubular epithelial cells and delaying renal interstitial fibrosis. |
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