论文部分内容阅读
【目的】观察糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化(TEMT)及氯沙坦干预对其的影响。【方法】雄性Wistar大鼠随机分为正常对照组和糖尿病模型组;后者经STZ诱导糖尿病模型成功后再随机分为糖尿病组和氯沙坦干预组[氯沙坦20mg/(kg·d)]。分别于第8周和第16周时每组各处死5只大鼠。测定24h尿蛋白排泄量、血肌酐;留取肾组织作HE和Masson染色,观察肾小管间质损伤指数、肾间质胶原面积;免疫组织化学法检测肾小管上皮细胞α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和转化生长因子-β1(TGF-β1)表达,并作半定量分析。【结果】①与对照组相比,糖尿病模型组大鼠肾小管间质损伤指数和肾间质胶原面积明显增加(P<0.01);②糖尿病组大鼠肾小管上皮细胞α-SMA、Vimentin和TGF-β1阳性表达均显著高于对照组,α-SMA表达和TGF-β1表达呈正相关(rs=0.810,P<0.01)。③氯沙坦组尿蛋白排泄量、肾小管间质损伤和间质纤维化程度较糖尿病组减轻,肾小管上皮细胞α-SMA、Vimentin与TGF-β1表达强度较糖尿病组显著下调(P<0.01)。【结论】①糖尿病大鼠肾脏病理进程中存在TEMT;②氯沙坦可下调糖尿病大鼠肾小管上皮细胞TGF-β1、Vimentin、α-SMA表达,阻抑糖尿病肾小管上皮细胞发生TEMT而发挥肾脏保护作用。
【Objective】 To observe the effects of losartan on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) in diabetic rats. 【Methods】 Male Wistar rats were randomly divided into normal control group and diabetic model group. The latter group was randomly divided into diabetic group and losartan group [losartan 20 mg / (kg · d) ]. At the 8th week and the 16th week, 5 rats were killed in each group. 24h urinary protein excretion and serum creatinine were measured; renal tissue was collected for HE and Masson staining, tubulointerstitial injury index, interstitial collagen area; immunohistochemical detection of renal tubular epithelial cells α-smooth muscle actin ( α-SMA, Vimentin and transforming growth factor-β1 (TGF-β1) expression, and semi-quantitative analysis. 【Results】 ①Compared with the control group, the indexes of tubulointerstitial injury and the area of interstitial collagen in diabetic model group were significantly increased (P <0.01); ② The expressions of α-SMA, Vimentin and The positive expression of TGF-β1 was significantly higher than that of the control group. The expression of α-SMA was positively correlated with the expression of TGF-β1 (rs = 0.810, P <0.01). ③ The urinary protein excretion, tubulointerstitial injury and interstitial fibrosis in losartan group were lower than those in diabetic group, and the expression of α-SMA, Vimentin and TGF-β1 in renal tubular epithelial cells was significantly lower than that in diabetic group (P <0.01) ). 【Conclusion】 There is TEMT in the pathological process of kidney of diabetic rats; ② Losartan can down-regulate the expression of TGF-β1, Vimentin and α-SMA in diabetic rat renal tubular epithelial cells and inhibit the occurrence of TEMT in diabetic renal tubular epithelial cells; Protective effects.