洛伐他汀对肾病大鼠肾小球硬化的影响及机制-儿科学专业毕业论文.docxVIP

摘要目的：肾小球硬化是多种原因引起的肾小球损伤后出现的共同的转归， 摘要 目的：肾小球硬化是多种原因引起的肾小球损伤后出现的共同的转归， 病理生理为促进细胞外基质(ECM)增生和降解ECM的因子失衡。腊质代谢 紊乱是引起和促进肾小球硬化的危险条件之一。本课题旨在通过阿霉素肾 病大鼠肾小球硬化模型的建立，并应用洛伐他汀治疗，观察其对血脂、尿 蛋白的影响，以及对促进ECM积聚的细胞因子TGF—B 1、PDGF—BB和TIMP一1 表达的影响，探讨洛伐他汀延缓肾小球硬化的作用机制。 方法：24只雄性Wistar大鼠，随机平均分为3组，即正常对照组(A 组)，未治疗组(B组)，治疗组(C组)。B组、C组按5mg／kg于尾静脉注 射阿霉素，A组注射等量生理盐水，注射阿霉素后次日A组给予普通饲料喂 养，B组给予高胆圄醇饲料喂养，c组给予高胆固醇饲料+洛伐他汀(每天 4mg／kg)喂养。留取尿液及血液标本测定24小时尿蛋白含量和血生化测 定，12周后处死大鼠，切取右肾用于肾脏病理分析，免疫组化法检测肾组 织TGF—B l、PDGF—BB、TIMP一1的表达水平。 结果：①我们成功地建立了阿霉素肾病。肾小球硬化大鼠模型。②从实 验第2周至实验末，B、C两组大鼠24小时尿蛋白排泄量均高于A组，第5 周后c组尿蛋白排泄量低于B组。⑨实验第6周，B、c组皆出现低蛋自血 症和高胆固醇血症。第12周，C组血白蛋白、HDL显著高于B组，而CH、 TG、LDL低于B组。④B组多数肾小球呈节段性硬化，肾小管损伤，肾小 球硬化指数及泡沫细胞数量明显高于C组。⑤B、c维TGF—B l、PDGF—BB、 TIMP-I表达强于A组，而且c组表达弱于B组。⑥血ch分别与GSI和含 有泡沫细胞肾小球的百分率成正相关(y=0．86，0．88，P值均(O．01)。GSI 和泡沫细胞肾小球的百分率亦成正相关(Y=O．98，P值0．01)。GSl分别 与TGF-Bl、PDGF—BB和TIMP—l的表达成正相关(Y=0．89，0．93，0．96， P值均O．01)。 结论：在行高脂饮食阿霉素肾病大鼠肾小球硬化模型中，洛伐他汀除 具有降血脂、减少尿蛋白的作用外，还可能部分通过减少促进ECM积聚的 U ABSTRACTObjective：Glomerulosclerosis(GS)is ABSTRACT Objective：Glomerulosclerosis(GS)is the same effects which is caused by many reasons after glomeruli injury．The pathophysiological basis is the unbalanced oftwo sort factors which affect the Extracelluarmatrix(ECM)．The disorders of lipid metabolism is one of dangerous factors of GS．The purpose of our investigation is to establish the GS model which induced by adriamycin and hi曲cholesterol dieLuse HRI treatment，observe the effects on the blood lipid and the index of GS(GSI)，and the changes in the two sort factors which effect ECM．In all，it can further explore lovastatin possible mechanism which ameliorate GS． Methods：The 24 male wistar rats were randomly divided into three groups normal control group(A)、non-treated nephropathy group(B)、lovastatin—treated group(C)，and there were 8 rats in each group．Group A rats were fed a standard chow,Group B rats were fed high cholesterol diet．Group C rats were fed high cholesterol diet and supplied lovastatin as a dose of 4mg／kg daily．At the fist time，the ra