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 45 min 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 ， 5 d 组，且每个组均为 8 只大鼠；而 C 组和 S 组只观察 1 d 作为对照。手术造模前 3 d 开始给药， S 组和 IRIS 组给予西罗莫司，负荷剂量为 9 mg·kg-1 ，以后每天灌胃 1 次，维持剂量为 3 mg·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， 1 d 时，肌酐和内皮素显著降低 (<>P<0.05) ； 3 d 时两组肌酐、内皮素和一氧化氮的含量无明显差异； 5 d 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 1 d 时的肾功能，但对 3 ， 5 d 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。
Abstract
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.
关键词
西罗莫司 /
肾缺血再灌注损伤 /
肾功能
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Key words
sirolimus /
renal ischemia/reperfusion injury /
renal function
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参考文献
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（ 收稿日期 ： 2008-12-27 ）
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