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目的:探讨过氧化物酶体增殖物激活受体激动剂罗格列酮(RSG)对单侧输尿管梗阻(UUO)大鼠肾间质炎症的保护作用及其作用机制。方法:将雄性SD大鼠随机分成五组,①假手术对照组(Sham);②假手术+大剂量罗格列酮[30mg/(kg·d]组(Sham+RSG);③UUO不用药组(UUO);④UUO+小剂量罗格列酮[5mg/(kg·d)]治疗组(UUO+RSG1);⑤UUO+大剂量罗格列酮[30mg/(kg·d)]治疗组(UUO+RSG2)。除假手术对照组外,其余各组根据不同干预时间细分为3天、7天、14天亚组。观察RSG对肾小管间质纤维化的影响及图象分析的不同时间点梗阻侧肾间质ED1阳性巨噬细胞浸润数量;肾皮质炎性因子单核细胞趋化蛋白1(MCP1)、肿瘤坏死因子1(TNFα)、巨噬细胞集落刺激因子(MCSF)等的mRNA表达(逆转录聚合酶链反应检测);及ELISA检测肾皮质MCP1蛋白含量。结果:14天时RSG能显著减轻UUO模型肾小管间质纤维化指数。与UUO组相比,RSG组使UUO7天及14天时梗阻侧肾间质ED1阳性的巨噬细胞浸润数显著减少;MCP1mRNA水平和蛋白水平表达均显著降低;MCSFmRNA及TNFαmRNA表达显著下调。结论:RSG能抑制UUO模型大鼠肾间质炎症和纤维化,减少肾间质巨噬细胞浸润和肾皮质炎性细胞因子表达。
Objective: To investigate the protective effect of peroxisome proliferator-activated receptor agonist rosiglitazone (RSG) on renal interstitial inflammation in unilateral ureteral obstruction (UUO) rats and its mechanism. Methods: Male Sprague-Dawley rats were randomly divided into five groups: ① sham operation control group (Sham); ② sham operation + high-dose rosiglitazone 30 mg / (kg · d] group (Sham + RSG) (UUO); ④UUO + low-dose rosiglitazone [5mg / (kg · d)] treatment group (UUO + RSG1); ⑤UUO + high dose rosiglitazone [30mg / (kg · d) ) .Except sham operation control group, the other groups were divided into 3 days, 7 days and 14 days subgroup according to different intervention time.Observed the effect of RSG on tubulointerstitial fibrosis and image analysis of obstruction at different time points The number of infiltrating ED1 positive macrophages in renal interstitium; the mRNA expression of MCP1, TNFα and MCSF RT-PCR was used to detect MCP1 protein in renal cortex.Results: RSG could significantly reduce the tubulointerstitial fibrosis index in UUO model at 14 days.Compared with UUO group, RSG group decreased UUO 7 and 14 days The infiltration of ED1-positive macrophages in obstructive lateral renal interstitium was significantly reduced; the expression of MCP1 mRNA and protein were significantly decreased; the expressions of MCSF mRNA and TNFα mRNA were significantly down-regulated. Discussion: RSG can inhibit renal interstitial inflammation and fibrosis in rats with UUO, reduce renal interstitial macrophage infiltration and renal cortical inflammatory cytokines expression.