氯沙坦对糖尿病大鼠肾脏α-actinin-4表达的影响及意义

目的研究糖尿病大鼠肾脏α-辅肌动蛋白-4(α-acti-nin-4)表达的变化以及血管紧张素Ⅱ(AngⅡ)Ⅰ型受体(ATⅠ)拮抗剂氯沙坦(losartan)的调节作用。方法♂SD大鼠随机分为对照组(N组)、糖尿病组(D组)和氯沙坦治疗组(DL组),每组10只,腹腔注射链脲佐菌素(STZ)诱发糖尿病大鼠模型,氯沙坦治疗组于造模成功后每日给予氯沙坦20mg·kg-1灌胃。8wk末电镜观察足细胞超微结构的变化;免疫组化、Western blot检测各组肾组织α-actinin-4蛋白的表达;半定量RT-PCR检测各组肾组织α-actinin-4mRNA的表达;应用放射免疫法检测肾组织AngⅡ的含量。结果D组大鼠肾重/体重、24h尿蛋白排泄量明显高于N组;肾组织α-actinin-4蛋白及mRNA的表达均明显低于N组。氯沙坦干预后可明显改善24 h尿蛋白与血肌酐水平,α-actinin-4蛋白及mRNA的表达水平明显高于D组。D组大鼠肾组织AngⅡ含量明显高于C组,但氯沙坦给药对其无影响。结论α-actinin-4表达降低参与了糖尿病肾病大鼠蛋白尿的发生,氯沙坦可以上调糖尿病大鼠肾脏α-actinin-4的表达,从而对肾脏起到保护作用。

The effect and significance of losartan on the expression of α-actinin-4 in diabetic rat kidneys

Aim To observe the expression of α-actinin-4 in the kidney in diabetic rats and the effect of losartan on it.Methods Diabetes was induced by injection of streptozotocin.Rats were randomly separated into three groups with 10 rats in each group: control group,diabetes group and diabetes treated with losartan group.Ultrastructure of the podocyte was observed by electron microscope and urinary protein excretion in 24 hours were determined after 8 weeks.The expression of α-actinin-4 protein was examined by immunohistochemistry and Wsetern blot.Expression of α-actinin-4 mRNA was examined by RT-PCR in the kidney.Radioimmunoassay was used to measure renal angiotensin Ⅱ.Results Increased ratio of kidney weight to body weight,urinary protein excretion in 24 hours were significantly attenuated by the treatment of losartan.Compared with those in control group,kidney protein and mRNA expression of α-actinin-4 were significantly decreased in diabetic rats,which were significantly up-regulated by losartan.Compared with the control group,the renal angiotensin Ⅱ of diabetic rats was markedly elevated up at week 8.Losartan has no effect on the renal angiotensin Ⅱ.Conclusion The decreased expression of α-actinin-4 takes part in the development of proteinuria in diabetic rats and losartan play a protective role in diabetic kidneys by up-regulating α-actinin-4.