绞股蓝总皂甙对梗阻性肾病大鼠TGF-β/Smad信号通路及CTGF表达的影响

Regulation of gypenosides on TGF-β/Smad signaling pathway and expression of connective tissue growth factor in unilateral ureteral obstruction rats with renal tubulointerstitial fibrosis

目的研究单侧输尿管结扎大鼠(UUO)肾组织中结缔组织生长因子(CTGF)、Smad7表达与肾间质纤维化之间的关系,以及绞股蓝总皂甙(GPs)对Smad7、CTGF的影响。方法采用UUO大鼠模型,将大鼠随机分为3组:假手术组、模型组、GPs组。假手术组和模型组仅给予标准饲料30 g,GPs组于术前3 d至术后14 d每天给予GPs 200 mg.kg-1.d-1灌胃,分别于第3、7、14 d处死各组大鼠。免疫组化法检测各组肾组织CTGF和Smad7的表达;RT-PCR方法检测各组Smad7 mRNA、CTGF mRNA含量;Masson染色评定各组肾小管间质损害程度。结果模型组CTGF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Smad7表达明显低于假手术组(P<0.01);GPs组CTGF及肾小管间质损伤指数随治疗时间降低,第7天下降最明显,而Smad7表达随时间增高,第7天升至最高。与模型组相比,各时间段均有显著差异(P<0.01)。结论UUO大鼠肾组织中CTGF的表达可能通过TGF-β/Smad信号通道进行调节;绞股蓝总皂甙可以通过上调Smad7的表达来抑制结缔组织生长因子表达,进而遏制肾纤维化的进展。

Objective To investigate the expression transforming growth factorβ1 （TGF-β1）, Smad7 and connective tissue growth factor （CTGF） in rats with renal tuhulointerstitial fibrosis and the effects of Gypenosides （GPs） treatment on expression of TGF-β, Smad7 and CTGF. Methods Unilateral ureteral Obstruction （UUO） rat animal models were used and the rats were divided into GPs group （Gypenosides 200 mg · Kg^-1· d^-1 by gastric gavage from 3d before the obstruction to 14 days after the induction）, model group and sham operated group. The expression of TGF-β1, Smad7 and CTGF in the obstructed kidneys was assessed by RT-PCR, immunohistochemistry and HE staining methods after 3, 7, and 14d respectively. The degree of tubulointerstitial damage was scored by Masson staining methods. Results Compared with the sham operated group, the expressions of TGF-β1, CTGF mRNA and protein were markedly increased in UUO group, and the expression of Smad7 mRNA and protein was markedly decreased （ all P 〈0.01 ）. Compared with model group, the expression of Smad7 mRNA was markedly increased and the expression of CTGF was markedly decreased in GPs-treated group. The degree of tubulointerstitial damage was increased after unilateral ureteral obstruction. The expression of Smad7 increased and the degree of tubulointerstitial damage decreased with the treatment of GPs. Conclusions The expression of CTGF in UUO rats may be regulated by TGF-β/Smad signaling path. The GPs inhibits the expression of CTGF through up-regulation of Smad7, and inhibits the progression of renal tubulointerstitial fibrosis.