冬虫夏草对糖尿病肾病模型鼠肾组织转化生长因子β_1、结缔组织生长因子表达的影响

Effect of cordceps sinensis on expressions of TGF-β_1 and CTGF in Rats with diabetic nephropathy

目的:观察冬虫夏草制剂对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)模型大鼠肾组织转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)表达的影响,探讨冬虫夏草制剂抗肾纤维化的作用机制。方法:45只Wistar大鼠随机分为正常组、DN模型组、冬虫夏草组。虫草组予人工冬虫夏草粉5·0g/(kg·d)进行干预。第2、4、6周处死大鼠(每组5只)。检测24h尿蛋白定量、血肌酐(SCr)水平和肾组织病理变化;用免疫组化法检测肾组织CTGF、Ⅳ胶原(ColⅣ)的表达;用RT-PCR法检测肾组织TGF-β1、CTGF、ColⅣmRNA的表达。结果:DN模型组尿蛋白排泄明显增加(P<0·01),SCr水平上升(P<0·05)同时肾组织内细胞基质增多,TGF-β1、ColⅣ和CTGF出现高表达。冬虫夏草制剂干预,与DN模型组比较,虫草干预组尿蛋白排泄明显减少,SCr水平降低,肾组织病理改变减轻,并且肾组织中TGF-β1、CTGF、ColⅣ表达均有下调(P<0·05或P<0·01)。结论:冬虫夏草制剂对DN具有一定肾保护作用及抗肾小球纤维化的作用,其作用机制可能是通过使TGF-β、CTGF的表达下调而实现的。

Objective：To observe the effects of cordceps sinensis （CS） on the expression of TGF--β1 and CTGF in the renal tissue of diabetic nephropathy（DN） rats, and to investigate the anti-fibrosis mechanism of CS. Methodology： Fourty-five male Wistar rats were randomly divided into normal control group, DN group and treated group with CS [ 5.0 g/（kg-d） ]. At week 2, week 4 and week 6, five rats of three groups were sacrificed to test renal fibrotic injury, serum creatinine （SCr） , and 24hr urinary protein count. The expression of TGF-β1 , CTGF and Collagen IV were examined by immunohistochemical technique and RT-PCR. Results：Compared with DN model group, the levels of SCr, 24h urinary protein excretion, and glomerular fibrosis was reduced significantly in CS treatment group （ P 〈 0. 05 or P 〈 0. 01 ）. At the same time, the expression of TGF-β, CTGF, Col IV was significantly decreased in CS treated group （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion：Cordceps sinensis may be play a role in renoprotection and anti-fibrosis in rats with DN, and it maybe contribute to reducing the expression of TGF-β1 and CTGF.