坎地沙坦对糖尿病大鼠肾小管上皮细胞表型转化的影响

目的:探讨坎地沙坦对糖尿病大鼠肾小管上皮细胞α-平滑肌肌动蛋白(α-SMA)和波形蛋白(Vi mentin)表达的影响。方法:雄性SD大鼠腹腔注射链脲佐菌素(STZ,60 mg/kg)诱导糖尿病模型后,随机分为糖尿病组和坎地沙坦组。正常对照组仅注射等剂量溶媒。16周后观察各组血糖(BS)、肾重/体重(KW/BW)、24h尿白蛋白排泄率(AER)、肌酐清除率(Ccr)。PAS染色观察肾脏病理形态学变化;免疫组化观察肾组织α-SMA和Vi mentin表达的变化。结果:与对照组相比,糖尿病组大鼠BS、KW/BW、AER、Ccr及间质纤维化损伤均显著上升(P<0.01),坎地沙坦组上述指标除血糖外均明显改善,与对照组相比,α-SMA和Vi mentin在肾小管上皮表达均明显上调(P<0.01),结果表明,坎地沙坦治疗阻止了二者在糖尿病大鼠肾脏的高表达。结论:坎地沙坦能显著下调糖尿病大鼠肾小管α-SMA和Vi mentin表达,阻抑肾小管上皮细胞转分化。

Effects of Candesartan on Renal Tubule Epithelial Cells Transdifferentiation in Diabetic Rats

Objective：To investigate the effect of candesartan on the expression of alpha-smooth muscle actin （α-SMA） and vimentin in renal tubular epithelial of diabetic rats. Methods：Diabetes was induced in male SD rats by intraperitoneal administration of streptoztocin （STZ） 60mg/kg body weight. The rats then were randomized to diabetic group and candesartan therapy group. The normal group rats were administrated only the same dose of citrate buffer. At the end of the 16th week, blood glucose （BS）, kidney weight/body weight （KWJBW）, urine albumin （UAlb）, and ereatinine clearance rate （Ccr） were determined. The renal histopathology was observed by PAS staining. Further biochemical analysis of α-SMA and virnentin was provided using immunostaining. Results： Compared with normal group, BS, KW/ BW, UAlb, Ccr, and interstitial fibrotic lesions were increased in diabetic group. Treatment with candesartan could improve these parameters except 13S. Compared with normal group, expression of α-SMA and vimentin in tubular epitheliar cells were highly up-regulated in diabetic group（P〈0. 01）. Administration of candesartan prevented the high expression of α-SMA and vimentin in renal tubular epitheliar cells of diabetic rats. Conclusion： Candesartan can down-regulate the expression of α-SMA and vimentin in diabetic renal tubular epitheliar cells and restrain the process of epithelial transdifferentiation in diabetic rats.