Rapamycin markedly slows disease progression in a rat model of passive Heymann nephritis / 中国病理生理杂志

ABSTRACT

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 groupscontrol 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 .