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目的观察西罗莫司对大鼠肾缺血再灌注损伤的影响,并初步探讨其机制。方法采用健康雄性SD大鼠,切除右肾,夹闭左侧肾动脉45min制作肾缺血再灌注损伤模型。大鼠随机分为单纯假手术组(C),西罗莫司假手术组(S),肾缺血再灌注组(IRI),西罗莫司肾缺血再灌注组(IRIS),根据再灌注时间不同,IRI组和IRIS组又分为1,3,5d组,且每个组均为8只大鼠;而C组和S组只观察1d作为对照。手术造模前3d开始给药,S组和IRIS组给予西罗莫司,负荷剂量为9mg·kg-1,以后每天灌胃1次,维持剂量为3mg·kg-1,直至处死。C组和IRI组相应给予生理盐水,观察大鼠术后各时相点血清肌酐(Cr)、血浆内皮素、肾组织中一氧化氮及肾组织形态学的变化。结果假手术组中,西罗莫司能显著降低血清肌酐,明显提高肾组织一氧化氮的含量(P<0.01),而对血浆内皮素无明显影响。模型组中,IRIS组与IRI组相比,1d时,肌酐和内皮素显著降低(P<0.05);3d时两组肌酐、内皮素和一氧化氮的含量无明显差异;5d时肌酐无明显变化,但内皮素明显降低且一氧化氮的含量明显升高(P<0.05)。结论西罗莫司能明显改善肾缺血再灌注损伤后1d时的肾功能,但对3,5d时肾功能改善不明显,其改善肾功能的机制可能与内皮素及一氧化氮的作用有关。
Objective To observe the effect of sirolimus on renal ischemia-reperfusion injury in rats and to explore its mechanism. Methods Healthy male Sprague-Dawley rats were used to excise the right kidney and the left renal artery was implanted for 45 minutes to make a model of renal ischemia-reperfusion injury. The rats were randomly divided into sham operation group (C), sirolimus sham operation group (S), renal ischemia / reperfusion group (IRI) and sirolimus reperfusion group (IRIS) Irrigation time is different, IRI group and IRIS group is divided into 1,3,5 d group, and each group is 8 rats; while C group and S group only observed 1d as a control. The rats were given sirolimus at 3 days before surgery. Sirolimus was administered to S and IRIS groups. The loading dose was 9 mg · kg-1. The rats were orally gavaged once daily for 3 mg · kg-1 until the sacrifice was performed. Rats in group C and IRI were given normal saline, and the changes of serum creatinine (Cr), plasma endothelin, renal tissue nitric oxide and renal tissue morphology were observed at different time points after operation. Results In the sham operation group, sirolimus significantly reduced serum creatinine, and significantly increased the content of nitric oxide (P <0.01) in renal tissue, but had no effect on plasma endothelin. In the model group, creatinine and endothelin were significantly decreased in IRIS group compared with IRI group (P <0.05) at 1 day. There was no significant difference in creatinine, endothelin and nitric oxide between the two groups at 3d and no significant difference at 5 days Change, but the endothelin was significantly decreased and the content of nitric oxide was significantly increased (P <0.05). Conclusion Sirolimus can significantly improve renal function at 1 day after renal ischemia-reperfusion injury, but there is no obvious improvement on renal function at 3,5 days. The mechanism of improving renal function may be related to the effects of endothelin and nitric oxide .