雷帕霉素减缓大鼠被动Heymann肾炎的进展  

Rapamycin markedly slows disease progression in a rat model of passive Heymann nephritis

作　　者：杨凤杰[1] 周建华[1] 吕倩影[1] 蒲金赟 张瑜[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,湖北武汉430030

出　　处：《中国病理生理杂志》2014年第9期1661-1665,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81100514;No.30772360);教育部博士点基金资助项目(新教师类)(No.20110142120017)

摘　　要：目的:观察雷帕霉素对大鼠被动Heymann肾炎(PHN)的影响,并探讨自噬在其中的作用。方法:雄性SD大鼠随机分为3组,即对照组、PHN模型组和雷帕霉素治疗组。以造模后第21天为观察结点,采用全自动生化分析仪测定24 h尿蛋白总量、血尿素氮和血清肌酐,过碘酸-六次甲基四胺银染色观察肾脏病变,Weibel-Gomez点计数方法计数足细胞数量,免疫荧光染色检测肾小球内C5b-9的沉积,免疫组化染色观察caspase-3的表达,Western blotting检测肾小球LC3的表达。结果:雷帕霉素明显减轻PHN模型大鼠的蛋白尿排出(P<0.05),同时各组大鼠的肾功能均正常,其间无显著差异;雷帕霉素使PHN大鼠肾小球基底膜增厚的程度和范围有所减轻;雷帕霉素明显改善PHN大鼠足细胞缺失情况,减少足细胞凋亡;雷帕霉素可增强肾小球内固有细胞的自噬水平。结论:在PHN的病变过程中,适度增强自噬减少足细胞凋亡,减轻肾脏病变和缓解蛋白尿,可能是雷帕霉素减缓大鼠PHN进展的重要机制之一。AIM： To determine the effect of rapamycin on the progression of passive Heymann nephritis（ PHN）,and whether autophagy is involved in this process. METHODS： Male Sprague-Dawley rats（ n =24） were randomly divided into 3 groups： control group,PHN group and rapamycin treatment group. The rat PHN model was induced by injection of anti-Fx1 A serum through penile vein,and all rats were sacrificed on day 21. Automatic biochemical analyzer was used to detect 24 h urine protein,blood urea nitrogen and serum creatinine. Renal damage was observed through periodic acid-silver methenamine staining. The number of podocyte was estimated by Weibel-Gomez method. The glomerular deposition of C5b-9,the expression of caspase-3 and expression of autophagy marker LC3 in glomeruli were examined by immunofluorescence staining,immunohistochemical staining and Western blotting,respectively. RESULTS： Rapamycin significantly reduced proteinuria in the PHN rats（ P〈 0. 05）,while the renal functions in 3 groups were normal,without significant difference. Although rapamycin limited weight gain in the rats,the health of the rats during drug treatment was not affected. Rapamycin retarded glomerular basement membrane thickening in the PHN rats. Rapamycin significantly reduced the podocyte deletion by preventing podocyte apoptosis. Rapamycin enhanced the level of autophagy of glomerular inherent cells. CONCLUSION： In the disease process of PHN,appropriate strength of autophagy plays a protective role.Rapamycin appropriately enhances autophagy and prevents podocyte apoptosis,thus reducing nephropathy and proteinuria.This may be one of the important mechanisms of rapamycin to slow down the progress of PHN.

关 键 词：自噬 足细胞 雷帕霉素 被动Heymann肾炎 

分 类 号：R363.2[医药卫生—病理学]