白藜芦醇对慢性肾衰竭大鼠肾脏组织BMP-7、TGF-β_1、Smads信号通路表达的影响

Effect of Resveratrol on the Expression of BMP-7,TGF-β_1 and Smads Signaling Pathway in Renal Tissue of Rats with Chronic Renal Failure

目的:观察白藜芦醇对慢性肾衰竭(chronic renal failure,CRF)大鼠肾脏组织BMP-7、转化生长因子-β_1(transforming growth factor-β_1,TGF-β_1)、Smads信号通路表达的影响,分析其延缓CRF进展及抗肾间质纤维化的机制。方法:采用腺嘌呤制作CRF大鼠模型,随机分为模型组、氯沙坦组、白藜芦醇低剂量组和白藜芦醇高剂量组,另取8只正常大鼠作为空白对照组。观察大鼠治疗后血清肌酐、尿素氮水平;采用RT-PCR法检测肾脏组织内TGF-β_1mRNA表达水平,采用免疫组织化学法检测BMP-7、TGF-β_1、Smad6的蛋白表达,采用Western blot检测BMP-7、Smad6蛋白的表达,比较大鼠肾脏组织BMP-7、GF-β_1、Smads信号通路表达。结果:氯沙坦组、白藜芦醇低剂量组、白藜芦醇高剂量组肌酐、尿素氮均明显低于模型组(P<0.05);氯沙坦组、白藜芦醇低剂量组、白藜芦醇高剂量组TGF-β_1mRNA表达水平均明显低于模型组,差异有统计学意义(P<0.05);白藜芦醇低剂量组TGF-β_1mRNA表达水平低于氯沙坦组(P<0.05);与模型组比较,氯沙坦组、白藜芦醇低剂量组、白藜芦醇高剂量组BMP-7、Smad6蛋白表达均有提高,差异有统计学意义(P<0.05);与氯沙坦组比较,白藜芦醇低剂量组BMP-7、Smad6蛋白表达提高更为明显(P<0.05);白藜芦醇低剂量组和高剂量组BMP-7、Smad6蛋白比较,差异有统计学意义(P<0.05)。结论:白藜芦醇通过增强BMP-7和Smad6蛋白的表达,减弱TGF-β_1的表达,对TGF-β_1信号向核内转导的通路进行抑制,起到减轻肾间质纤维化、保护肾脏功能的目的。

Objective： To investigate the effect of resveratrol on the expression of BMP-7,transforming growth factor-β1（ TGF-β1）and Smads signaling pathway in renal tissue of rats with chronic renal failure（ CRF）,and to research the mechanism of delaying CRF progression and antirenal interstitial fibrosis. Methods： 55 rats were selected as the subjects,and chronic renal failure rats were produced by adenine. The rats were divided into blank control group,model group,losartan group,resveratrol low-dose group and resveratrol high-dose group,the changes of serum creatinine（ Cr） and blood urea nitrogen（ BUN） were observed after treatment. The expression of TGF-β1 mRNA in renal tissue was detected by RT-PCR method,the protein expression of BMP-7,TGF-β1 and Smad6 protein was detected by immunohistochemical method,the expression of BMP-7 and Smad6 protein was detected by Western blot,and the expression of BMP-7,GF-β1 and Smads signal pathway in renal tissue of rat was compared. Results： The levels of Cr and BUN in the high-dose and the low-dose group of resveratrol and the losartan group were significantly lower than that in the model group（ P 〈0. 05）; compared to the model group,TGF-β1 mRNA expression level in the losartan group,low dose and high dose of resveratrol was significantly decreased,and the difference was statistically significant（ P 〈0. 05）; TGF-β1 mRNA expression level in the low dose group of resveratrol was lower than the losartan group（ P〈 0. 05）. Compared with the model group,BMP-7,Smad6 protein expression in the losartan group,low dose and high dose group of resveratrol were increased,the difference was statistically significant（ P 〈0. 05）; compared with the losartan group,BMP-7,Smad6 protein expression improvement in the low dose group of resveratrol was more obvious with statistical significance（ P 〈0. 05）; BMP-7 and Smad6 proteins of resveratrol low dose group and high dose group（ P〈 0. 05）. Conclusion： Resveratrol can inhibit the expression of TGF-beta 1 by inhibiting the expression of BMP-7 and Smad6 protein,and inhibiting the transduction pathway of TGF-beta 1 signal into the nucleus,so as to alleviate renal interstitial fibrosis and protect renal function.