1.Department of Pharmacology, Wenzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University, Wenzhou, 325000; 2.Department of Nephrology, Wenzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University, Wenzhou, 325000; 3.Department of Nephrology, Wenzhou Geriatric Hospital, Wenzhou, 325000
ZHAO Yanyun,XIANG Xielong,JIAN Yijuan, et al. Effect of Benazepril on expression of TGF-β1, α-SMA and NOX4 in renal tissues of rats with unilateral ureteral obstruction[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2017, 47(9): 648-653.
Abstract：Objective: To observe the effects of Benazepril on expression of TGF-β1, α-SMA, NOX4 in renal tissues of rats with unilateral ureteral obstruction (UUO) and investigate the mechanism of it in renal interstitial fibrosis. Methods: The male Sprague-Dawley (SD) rats (54 cases) were randomly divided into Sham-operated group, model group and Benazepril treated group, 18 rats in each group. The benazepril group was given
1.6 mg/kg intragastric administration 1 times a day, and the model group and the sham operation group were given 10 mL/kg 0.9% sodium chloride solution gavage 1 times a day, model group and the benazepril group were ligated left ureter to establish UUO models. At days 7, 14 and 21, six rats in each group were sacrificed. Their left surgery renal tissues were collected for pathological examination. The pathological changes of the obstruction renal tissue were examined by Masson staining. The protein and gene expression of TGF-β1, α-SMA, NOX4 was detected by immunohistochemical staining respectively and NOX4 was detected by RT-PCR. Results: Compared with the Sham-operation group, the renal interstitial fibrosis degree of rats in other groups was increased (P<0.05), and aggratated as the ureteral obstruction time prolonged. Compared with the model group, after the treatment, the renal interstitial fibrosis degree decreased significantly (P<0.05). Compared with the Sham-operation group, the protein expression of TGF-β1, α-SMA, NOX4 in other group increased (P<0.05). Compared with the model group, after the treatment by Benazepril, the protein expression TGF-β1, α-SMA, NOX4 was down-regulated in the renal tissue (P<0.05). Conclusion: Benazepril may effectively retard kidney interstitial fibrosis by reducing the expression of TGF-β1, α-SMA, NOX4 to inhibit inflammatory of kidney.
[1] ZHANG L, WANG F, WANG L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey[J]. Lancet, 2012, 379(9818): 815-822.
[2] 罗婷, 程锦国, 简怡娟, 等. 清化固肾排毒方对UUO大鼠上皮细胞转分化的影响[J]. 上海中医药杂志, 2015, 49(11):71-78.
[3] DING Y, CHOI M E. Regulation of autophagy by TGF-β: emerging role in kidney fibrosis[J]. Semin Nephrol, 2014, 34(1): 62-71.
[4] RHYU D Y. Role of reactive oxygen species in TGF-β1 induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells[J]. J Am Soc Nephrol, 2005, 16(3): 667-675.
[5] STRUTZ F M. EMT and proteinuria as progression factors [J]. Kidney Int, 2009, 75(5): 475-481.
[6] HE J, XU Y, KOYA D, et al. Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney dis-ease[J]. Clin Exp Nephrol, 2013, 17(4): 488-497.
[7] 罗婷, 程锦国, 姜程曦, 等. 清化固肾排毒颗粒对肾纤维化大鼠Wnt通路Wnt1和β-catenin表达的影响[J]. 中草药, 2016, 47(6): 955-962.
[8] 陈宇, 罗婷, 陈薪薪, 等. 清化固肾排毒方对单侧输尿管 梗阻大鼠肾间质纤维化的保护作用及基质[J]. 中华中医药学刊, 2017, 35(5): 1268-1270.
[9] RAHAL A, KUMAR A, SINGH V, et al. Oxidative stress, prooxidants, and antioxidants:the interplay[J]. Biomed Res Int, 2014, 2014: 761264.
[10] BROWN D I, GRIENDLING K K. Nox proteins in signal transduction[J]. Free Radic Biol Med, 2009, 47(9): 1239-1253.
[11] MENN-JOSEPHY H, LEE C S, NOLIN A, et al. Renal interstitial fibrosis: an imperfect predictor of kidney disease progression in some patient cohorts[J]. Am J Nephrol, 2016, 44(4): 289-299.
