前列腺素E1脂微球载体制剂对多柔比星肾病大鼠结缔组织生长因子表达的影响

Effects of Lipo-PGE1 on the Expression of CTGF in Kidney of Rats with Adriamyc in Nephropathy

目的 :研究多柔比星肾病大鼠肾组织中结缔组织生长因子 (CTGF)表达 ,同时探讨前列腺素E1脂微球载体制剂 (Lipo PGE1)对其表达的影响。方法 :将 2 4只雌性SD大鼠 (体重 180～ 2 0 0g)随机分为对照组、多柔比星肾病模型组和多柔比星肾病Lipo PGE1治疗组 3组。采用尾静脉一次性注射多柔比星 7 5mg/kg的方法建立多柔比星肾病动物模型 ,第 8周开始Lipo PGE1治疗组给予尾静脉注射Lipo PGE1,用量 2 0 0 μg/ (kg·d)。 10周后处死全部大鼠 ,并观察肾组织病理改变 ,应用免疫组织化学方法和原位杂交技术检测CTGF在肾组织中的表达。结果 :Lipo PGE1治疗组大鼠肾小球硬化及基质增生程度比多柔比星肾病组明显减轻 ,免疫组织化学染色及原位杂交结果显示多柔比星肾病组较正常对照组肾小球和肾小管区CTGF蛋白及CTGFmRNA表达量明显增加 (P <0 0 5 )。Lipo PGE1治疗组肾小球和肾小管间质CTGF蛋白及CTGFmRNA表达量明显低于多柔比星肾病组 (P <0 0 5 )。结论 :多柔比星肾病组大鼠第 10周肾小球及肾小管间质尤其是肾小管间质区CTGF蛋白及CTGFmRNA表达量明显增加。Lipo PGE1延缓多柔比星肾病肾损害 ,其机制可能与通过下调CTGF的表达有一定关系 ,并且可能通过减少肾小球内细胞增生和细胞外基质 (ECM)沉积 ,延缓慢性肾脏疾病?

Objective: To investigate the effect of lipo prost ag landinE1 (prostaglandin E1 in corporated in lipid microspheres,Lipo-PGE1) on th e renal injury in adriamycin nephropathy rats and its possible mechanism. Methods: Twenty four female rats(180～200 g) were divided into 3 groups a t random:adriamycin nephropathy group(n=8),Lipo-PGE1 treated group (n=8 ) and normal control group (n=8). The adriamycin nephropathy model was induc ed by adriamycin i.v.at 7.5 mg/kg from vena caudalis. Lipo-PGE1 was given by i.v.at 200 μg/(kg·d) from the 8th to 10th weeks. The pathology of the rats wa s observed under optical microscopy. The expression of connective tissue growth factor(CTGF) were analyzed by immunohistochemistry and in situ hybridization.Results: Lipo-PGE1 significantly inhibited the progress of glomerula r sclerosis and the accumulation of the extracellular matrix, ameliorated the gl omerular histopathological changes. Expression of CTGF protein and CTGF mRNA in both glomerulars and tubles in treated group were much lower than that in untrea ted group(P<0.05).Conclusion: Lipo-PGE1 may inhibit the prog ression of impairment of adriamycin nephropathy by lightening glomerular scleros is and reducing the deposition of extra cellular matrix, which may be related to the down regulating expression of CTGF. [