栀子苷抗肾间质纤维化的作用机制研究*

Protective effect of Geniposide on renal interstitial fibrosis in rats*

摘要:

目的 通过转化生长因子-β1（TGF-β1）/Smad-2信号通路探讨栀子苷对肾间质纤维化的影响。方法 将SD大鼠随机分为对照组、正常大鼠灌胃组、模型组、30?mg/kg及15?mg/kg栀子苷组，每组8只。复制大鼠单侧输尿管结扎（UUO）肾间质纤维化模型，栀子苷组连续给予栀子苷14?d，对照组和模型组灌胃同体积的生理盐水；实验结束后，取大鼠结扎侧的肾脏，用HE染色观察肾间质纤维化病理情况；全自动生化仪检测血肌酐和尿素氮；ELISA检测大鼠血清中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量，Western blotting检测TGF-β1和Smad-2蛋白含量。结果 与模型组比较，30?mg/kg和15?mg/kg栀子苷组大鼠血清中炎症因子TNF-α和IL-1β含量均降低（P?<0.05），且呈剂量依赖性降低，MDA含量降低（P?<0.05），SOD活性升高（P?<0.05），且随着栀子苷浓度的增加而升高。与对照组比较，模型组肾脏组织中TGF-β1和Smad-2蛋白的表达增加（P?<0.05）；给予30和15?mg/kg的栀子苷后大鼠肾脏组织中TGF-β1和Smad-2蛋白表达降低（P?<0.05）。结论 栀子苷具有抗肾间质纤维化作用，其机制可能与通过抑制TGF-β1/Smad信号通路，降低炎症反应及氧化应激损伤有关。

Abstract:

Objective To investigate protective effect of Geniposide on renal interstitial fibrosis through TGF-β1/Smad-2 signaling pathway. Methods SD rats were randomly divided into control group (CG), and model group (MG), gavage group of normal rats, Geniposide group (30?mg/kg GG, or 15?mg/kg GG). Rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction. The rats in geniposide group were continuously given geniposide for 14 days, while rats in control group and model group were given the same volume of saline. Pathological changes of renal interstitial fibrosis were observed by HE staining. Serum creatinine and urea nitrogen were detected by automatic biochemical analyzer. IL-1β, TNF-α and SOD were determined by ELISA. TGF-1β and Smad-2 protein expression were determined by western blotting Results Serum levels of inflammatory factor TNF-α, IL-1β and MDA were significantly decreased (P?