【作者】 冯志平； 任斌； 于思源； 黎曙霞；

【机构】 中山大学附属第一医院药学部；

【摘要】 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。实验动物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天组,且每个组均为8只大鼠;而C组和S组只观察1天作为对照。手术造模前3天开始给药,S组和IRIS组给予西罗莫司,负荷剂量为9mg/kg,以后每天灌胃1次,维持剂量为3mg/kg,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天时,肌酐和内皮素显著降低(P<0.05);3天时两组肌酐、内皮素和一氧化氮的含量无明显差异;5天时肌酐无明显变化,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天时的肾功能,但对3、5天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。更多还原

【Abstract】 OBJECTIVE To investigate the effects of sirolimus on renal ischemia/reperfusion injury(IRI) in rats and its mechanism.METHODS The rats underwent right nephrectomy and the left renal arteries were gripped by vascular clamp for 45 minutes 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.8 rats in each subset.Medication started 3 days prior to the operation and continued daily till killing.Sirolimus was administered at a loading dose of 9 mg/kg followed maintenance doses of 3 mg/kg to rats by oral gavage.In the sham group and IRI group saline were given on the same schedule.The severity of the renal IRI was assessed by serum creatinine levels and renal histology,Nitrogen monoxidum(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.CONCLUSIONS Pretreatment with sirolimus may preserve renal ischemia-reperfusion injury on day 1,but the renal function was not improved significantly on days 3,5.This effect might be mediated through ET and NO.更多还原