摘要
【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 effect of Losartan on renal tubular epithelial cell myofibroblast transdifferentiation in diabetic rats and its possible mechanisms. [Methods]Fifty Wistar rats were randomly divided into two groups：Normal control group（ n = 10）, Diabetic mellitus models group （ n = 40） which were established by intraperitoneal injection of streptozotocin （60 mg·kg^-1 · d^-1 ）. After these models were successfully established,they were randomly divided into two groups ： diabetic group without therapy and diabetic group with Losartan （20 mg·kg^-1 · d^-1）. At eight and sixteen weeks after therapy with Lorsartan, the excretion of urinary protein and serum creatine were measured. Alpha smooth muscle actin（α-SMA）, vimentin and transforming growth factor-β1 （TGF-β1） in renal tubular epithelial cells were detected by immunohistochemistry of SP method. [Results]①The excretion of urinary protein in diabetic group was significantly higher than that in control and Losartan therapy groups. The tubulointerstitial injury and the accumulation of extracellular matrix protein in diabetic models were obvious. ②Compared with normal control group, α-SMA, vimentin and TGF-β1 in renal tubular epithelial cells showed gradually stronger positive in diabetic group （ P〈0. 01）. ③In comparison with diabetic group, Lorsartan could reduce excretion of urinary protein and delay the progression of tubulointerstitial fibrosis in diabetic rats, down-regulated the expression of α-SMA, vimentin and TGF-β1 in renal tubular epithelial cells （ P 〈0.01）. [Conclusion]①Renal tubular epithelial-myofibroblast transdifferentiation is an important event in the progress of diabetic nephropathy, which may be up-regulated by transforming growth factor-β1. ②Losartan may down-regulate expression of α-SMA, vimentin and TGF-β1 in diabetic renal tubular epithelial cells, can restrain the procession of epithelial-myofibroblast transdifferentiation. ③Losartan restraining the procession of epithelial-myfibroblast transdifferentiation may be a mechanism of protective effect on diabetic nephropathy.
出处
《医学临床研究》
CAS
2006年第10期1555-1558,1561,共5页
Journal of Clinical Research
关键词
糖尿病
实验性
上皮细胞
肾小管
洛沙坦
大鼠
diabetes mellitus, experimental
epithelial cells
kidney tubules
losartan
rats
