【作者】 黄杰；

【导师】 刘建社；

【作者基本信息】 华中科技大学 ， 内科学， 2008， 硕士

【摘要】 目的研究前列腺素E1脂微球载体制剂(prostaglandin E1 incorporated in lipid microspheres,Lipo-PGE1)对慢性肾衰竭大鼠肾脏的保护作用,并初步探讨其作用机制。方法5/6肾切除法建立大鼠慢性肾衰竭模型。将大鼠随机分为假手术组(10只)、肾衰竭模型组(10只)和Lipo-PGE1治疗组(10只)。8周后检测各组大鼠血尿生化指标,观察肾组织病理改变,RT-PCR法检测各组大鼠肾皮质中纤维连接蛋白(fibronectin,FN)、转化生长因子β1(transforming growth factor-β1,TGF-β1)和结缔组织生长因子(connective tissue growth factor,CTGF)mRNA的表达水平,免疫组织化学方法检测各组大鼠肾组织中FN、TGF-β1、CTGF和α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的蛋白表达水平。结果模型组大鼠24小时尿蛋白排泄量、血清尿素氮和肌酐水平显著高于假手术组(P<0.05,P<0.01),肾小球和肾小管-间质病变显著。经每天40μg/kg的Lipo-PGE1干预后,治疗组大鼠相关血尿生化指标较模型组有明显改善(P<0.05,P<0.01),肾脏病理改变明显减轻,肾小球硬化指数(Glomerulosclerosis index,GI)明显低于模型组(P<0.05),肾小管-间质病变减轻。与假手术组相比,模型组大鼠肾组织FN、TGF-β1、CTGF和α-SMA的表达明显上调(P<0.05,P<0.01)。治疗组大鼠经Lipo-PGE1干预后,FN、TGF-β1、CTGF和α-SMA的表达均有不同程度的抑制(P<0.05,P<0.01)。结论Lipo-PGE1对慢性肾衰竭大鼠肾脏具有保护作用,可能通过抑制肾小管上皮细胞-间充质细胞转分化,减少细胞外基质(extracellular matrix,ECM)的沉积,延缓肾脏纤维化的进展。更多还原

【Abstract】 Objective To investigate the renal protective effects of Lipo-prostaglandin E1 (prostaglandin E1 incorporated in lipid microspheres, Lipo-PGE1) on chronic renal failure in rats and its possible mechanism.Methods 30 male rats were divided into 3 groups randomly: sham operation group (n=10),chronic renal failure (CRF) group (n=10) and Lipo-PGE1 treated group (n=10). The animal model of chronic renal failure was induced by 5/6 nephrotomized. Lipo-PGE1 was given by i.v. at 40μg·kg-1·d-1 from the 6th week to the 8th week. At week 8, 24 hours urine protein excretion, blood urea nitrogen (BUN) and creatinine (Cr) were detected in the end of experiment. The pathological changes of kidney in rats were also observed through lightmicroscopy. The fibronectin (FN) mRNA, transforming growth factor-β1 (TGF-β1) mRNA and connective tissue growth factor (CTGF) mRNA expression in the renal cortex were detected by RT-PCR. The renal protein expressions of FN, TGF-β1, CTGF andα-smooth muscle actin (α-SMA) were analyzed by immunohistochemistry.Results 24 hours urine protein excretion, BUN and Cr in CRF group were significantly higher than sham operation group (P<0.05,P<0.01), the pathological changes of kidney in CRF group were significant. After the treatment with Lipo-PGE1, 24 hours urine protein excretion, BUN and Cr were improved obviously(P<0.05,P<0.01). The pathological changes of kidney were improved obviously in Lipo-PGE1 treated group. Glomerulosclerosis index (GI) in Lipo-PGE1 treated group was obviously lower than CRF group and the tubulointerstitial pathological changes of kidney in Lipo-PGE1 treated group were improved significantly. The expressions of FN, TGF-β1, CTGF andα-SMA in CRF group were obviously higher than sham operation group (P<0.05,P<0.01). After the treatment with Lipo-PGE1, the expressions of FN, TGF-β1, CTGF andα-SMA were also obviously inhibited in Lipo-PGE1 treated group compared with CRF group (P<0.05,P<0.01).Conclusion Lipo-PGE1 has some renal protective effects on chronic renal failure in rats. Lipo-PGE1 can inhibit epithelial-mesenchymal transdifferentiation and reduce the deposition of extracellular matrix. It may be an effective agent for the treatment of CRF.更多还原