绞股蓝总皂甙对单侧输尿管结扎大鼠肾组织结缔组织生长因子表达的影响

Effects of gypenosides on expression of connective tissue growth factor in UUO rats with renal tubulointerstitial fibrosis

目的:研究绞股蓝总皂甙(GPs)对单侧输尿管结扎(UUO)大鼠肾组织结缔组织生长因子(CTGF)表达及肾间质纤维化的影响。方法:采用UUO大鼠模型,将大鼠随机分为4组:假手术组、模型组、GPs组、缬沙坦组。假手术组和模型组仅给予标准饲料30g,GPs组和缬沙坦组于术前3d至术后9d每天分别给予GPs200mg/(kg·d)、缬沙坦24mg/(kg·d)灌胃,第9天处死各组大鼠。免疫组化法检测各组肾组织CTGF、转换生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达;RT-PCR方法检测各组CTGFmRNA含量;Masson染色评定各组肾小管间质损害程度。结果:模型组CTGF、TGF-β1、α-SMA的表达及肾小管间质损伤指数明显高于假手术组(P<0.01),而GPs组和缬沙坦组各项指标明显低于模型组(P<0.01);GPs组与缬沙坦组差异无显著性(P>0.05)。各项指标作相关分析,CTGF与肾小管间质损伤指数(r=0.756,P<0.01)、TGF-β1(r=0.879,P<0.01)、α-SMA(r=0.892,P<0.01)为正相关关系。结论:GPs可以抑制肾纤维化时CTGF表达,从而遏制肾纤维化的进展。

Objective To investigate the expression of connective tissue growth factor（CTGF） in rats with renal tubulointerstitial fibrosis and to observe the effects of gypenosides and valsartan treatment on CTGF protein production. Methods Unilateral ureteral obstruction （UUO） rat models were used. The expression of CTGF, TGF-β1, α-SMA in the obstructed kidneys was assessed by RT-PCR, immunohistochemistry and HE staining methods after nine days, respectively. At the same time, the degree of tubulointerstitial damage was scored by Masson staining methods. Results The levels of CTGF, TGF-β1, a-SMA in the UUO group increased remarkably as compared with the sham-operated group（P〈0. O1） and paralleled with the degree of tubulointerstitial damage. Compared with the model group, the levels of CTGF, and expression of TGF-β1, α-SMA were significantly decreased by both gypenosides and valsartan treatment. The protein level of CTGF was positive correlation with the index of TGF-β1 （r=0. 879, P〈0. 01）,α-SMA（r=0. 892, P〈0.01）, tubulointerstitial damage（r=0.756, P〈0.01 ） . Conclusions Gypenosides and valsartan may suppress the development of fibrosis, at least in part via down-regulating CTGF expression.