CAJ | 학술논문

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-Go-mez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。
목적：관찰뢰파매소대대서피동Heymann신염（ PHN）적영향，병탐토자서재기중적작용。방법：웅성SD대서수궤분위3조，즉대조조、PHN모형조화뢰파매소치료조。이조모후제21천위관찰결점，채용전자동생화분석의측정24 h뇨단백총량、혈뇨소담화혈청기항，과전산-륙차갑기사알은염색관찰신장병변，Weibel-Go-mez점계수방법계수족세포수량，면역형광염색검측신소구내C5b-9적침적，면역조화염색관찰caspase-3적표체， Western blotting검측신소구LC3적표체。결과：뢰파매소명현감경PHN모형대서적단백뇨배출（P＜0．05），동시각조대서적신공능균정상，기간무현저차이；뢰파매소사PHN대서신소구기저막증후적정도화범위유소감경；뢰파매소명현개선PHN대서족세포결실정황，감소족세포조망；뢰파매소가증강신소구내고유세포적자서수평。결론：재PHN적병변과정중，괄도증강자서감소족세포조망，감경신장병변화완해단백뇨，가능시뢰파매소감완대서PHN진전적중요궤제지일。
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 ran-domly divided into 3 groups:control group , PHN group and rapamycin treatment group .The rat PHN model was induced by injection of anti-Fx1A 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 per-iodic 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 LC 3 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 re-duced the podocyte deletion by preventing podocyte apoptosis .Rapamycin enhanced the level of autophagy of glomerular in-herent 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 .