OBJECTIVE To investigate the effects of sirolimus on renal ischemia/reperfusion injury (IRI) in rats and its mechanism. METHODS The rats right nephrectomy and the left renal arteries were gripped by vascular clamp for 45 min to induce renal ischemia/reperfusion injury. The rats were randomly divided into sham group（C）, sirolimus-treated sham group (S), IRI group and sirolimus-treated IRI group (IRIS ). The sham group and sirolimus-treated sham group were sacrificed at day 1, the other 2 groups at day 1,3,5 after kidney reperfusion, respectively. Eight rats were in each subset. Medication started 3 d prior to the operation and continued daily till killing. Sirolimus was administered at a loading dose of 9 mg·kg-1 followed maintenance doses of 3 mg·kg-1 to rats by oral gavage. In the sham group and IRI group saline were given with the same schedule. The severity of the renal IRI was assessed by serum creatinine levels and renal histology. Nitrogen monoxide(NO) in the renal tissue and endothelin(ET) in the plasma were measured. RESULTS Compared with those of sham group, sirolimus decreased creatinine significantly (P<0.01), but the change of NO was opposite (P<0.01). The levels of ET was not influenced. The serum creatinine and plasma ET of group IRIS were significantly lower than those of group IRI on day 1. There were no difference between 2 groups on day 3. On day 5 the content of NO in renal tissue was significantly increased (P<0.05), but plasma ET was opposite (P<0.05). The serum creatinine was not influenced. CONCLUSION Pretreatment with sirolimus may preserve renal ischemia-reperfusion injury on day 1, but the renal function was not improved significantly on day 3 and day 5. This effect might be related to ET and NO.
Key words
sirolimus /
renal ischemia/reperfusion injury /
renal function
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References
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（ 收稿日期 ： 2008-12-27 ）
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