Rapamycin aggravates the renal damage in rats with protein overload nephropathy and the protection of losartan
CHEN Yan, ZHENG Shao-ling, CHEN Bi-cheng, CAI Yong
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Transplantation Center, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China
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History+
Received
Revised
Published
2007-12-14
1900-01-01
2008-07-15
Issue Date
2008-07-15
Abstract
Objective To investigate the effects of rapamycin on renal tissue and function of rats with protein overload nephropathy and to explore the protective mechanism of losartan. Methods Experimental rat models with protein overload nephropathy, induced by intraperiotoneal injection of BSA (2. 0 g/d)into female Wistar rats, were divided into three groups: control group, rapamycin group(injected intraperitoneally with rapamycin) and losartan group(injected intraperitoneally with rapamycin and given orally with losartan). At different time points, the quantity of 24-hour urine protein and renal function were measured, and the morphologic changes of renal tissues were evaluated by HE staining and electron microscope. Results Both at day 7 and day 14, rats received BSA developed intense proteinuria. At day 7, compared with control group, 24-hour proteinuria increased markedly in rapamycin group (P<0.05). Nevertheless, proteinuria was notably alleviated in losartan group (P<0.05). At day 14, 24-hour-urine protein of rapamycin group was also significantly higher than that of the losartan group(P<0.05), but there was no significant difference between control group and losartan group(P>0.05). Proteinuria and intratubular albumin cast formation were alleviated notably in losartan group. The fusion of focal podocytes in rapamycin group was obvious in comparison with control group. Conclusions Rapamycin can agrravate proteinuria in rats with protein overload nephropathy through changing the barrier of glomerular filtration by damaging podocytes. Furthermore, losartan can alleviate severe proteinuria induced by rapamycin.
CHEN Yan;ZHENG Shao-ling;CHEN Bi-cheng;CAI Yong.
Rapamycin aggravates the renal damage in rats with protein overload nephropathy and the protection of losartan[J]. Chinese Journal of Nephrology, 2008, 24(7): 504-507.