白藜芦醇对肾功能衰竭大鼠timp-1mRNA、BAX及wnt4蛋白表达的影响

Effect of resveratrol on the expression of timp-1mRNA、BAX and wnt4 protein in rats with renal failure

目的:探讨白藜芦醇对肾功能衰竭大鼠肾脏基质金属蛋白酶组织抑制因子-1 (tissue inhibitors of metalloproteinases-1,TIMP-1)mRNA、凋亡调节因子Bax和Wnt4蛋白表达的影响。方法:选取60只SD大鼠,随机分为空白对照组(A组)、模型组(B组)、氯沙坦组(C组)、低剂量白藜芦醇组(D组)和高剂量白藜芦醇组(E组),每组14只。除空白对照组外,其余各组大鼠均应用腺嘌呤灌胃法制作慢性肾衰竭大鼠模型,建模成功后,对氯沙坦组、低剂量白藜芦醇组和高剂量白藜芦醇组大鼠分别给与氯沙坦、白藜芦醇进行治疗。应用HE染色对各组大鼠的肾组织细胞形态结构进行观察,检测并比较各组大鼠肾脏组织timp-1mRNA、Bax mRNA、Bax蛋白及Wnt4蛋白表达情况。结果:HE染色显示B组大鼠肾脏组织存在显著的病理学改变,而C、D、E组大鼠较模型组有显著改善。B组大鼠血肌酐、尿素氮水平显著高于A组,白蛋白水平显著低于A组,差异具有统计学意义(P<0.05);C、D、E组大鼠的血肌酐、尿素氮水平则显著低于B组,白蛋白水平显著高于B组,差异具有统计学意义(P<0.05)。B组大鼠肾脏timp-1基因、Bax基因mRNA表达水平显著升高,Bax和Wnt蛋白表达水平也显著升高,而C、D、E组大鼠肾脏timp-1基因、Bax基因mRNA和Bax和Wnt蛋白表达水平较B组则明显降低,以D组降低幅度最大,D组与C组、D组与E组比较也存在显著差异(P<0.05),E组和C组比较则无明显差异(P>0.05)。结论:低剂量的白藜芦醇通过抑制timp-1、Bax基因和Wtn4蛋白的表达来发挥减轻肾脏纤维化损害、抑制肾组织细胞凋亡和保护肾脏的作用,从而可延缓慢性肾衰竭的进展。

Objective:To investigate the effect of resveratrol on the expression of tissue inhibitors of metalloproteinases-1(TIMP-1)mRNA,Bax and Wnt-4 protein in kidney of rats with renal failure.Methods:Sixty SD rats were randomly divided into control group(group A),model group(group B),losartan group(group C),low-dose resveratrol group(group D)and high-dose resveratrol group(group E),with 14 rats in each group.Except for the blank control group,the rats in the other groups were given adenine intragastric administration to make rat models with chronic renal failure.After successful modeling,the rats in losartan group,low-dose resveratrol group and high-dose resveratrol group were given losartan and resveratrol respectively.HE staining was used to observe the morphological structure of renal tissue cells of rats in each group.The expressions of TIMP-1 mRNA,Bax mRNA,Bax protein and Wnt4 protein were detected and compared.Results:HE staining showed that there were significant pathological changes in the kidney tissues of rats in group B,while those in group C,D and E were significantly improved compared with those in model group.The levels of serum creatinine and urea nitrogen in group B were significantly higher than those in group A but albumin was significantly lower than that in group A(P<0.05).The levels of serum creatinine and urea nitrogen in group C,D and E were significantly lower than those in group B while albumin was significantly higher than that in group B(P<0.05).The expression levels of TIMP-1 gene and Bax gene mRNA in kidney of rats in group B were significantly increased,and the expression levels of Bax and Wnt protein were also significantly increased.The expression levels of TIMP-1 gene and Bax gene mRNA as well as Bax and Wnt protein in kidney of rats in group C,D and E were significantly lower than those of rats in group B,with the greatest decrease in group D.The differences between group E and group D as well as bewtween group C and group D were significant(P<0.05).However,the difference between group E and group C was not significant(P>0.05).Conclusion:Low dose resveratrol can alleviate renal fibrosis damage,inhibit apoptosis and protect kidney by inhibiting the expression of TIMP-1,Bax gene and Wtn4 protein,thus delaying the progression of chronic renal failure.