摘要
目的 探讨瑞芬太尼调控Fas凋亡信号通路对大鼠肾脏缺血再灌注（IR）损伤的作用及其机制.方法 采取随机数字表法将SD大鼠随机分为假手术组（S组）、缺血再灌注对照组（IR组）和实验组（R组）,每组20只.IR组和R组以夹闭双侧肾动脉45 min后恢复再灌注制备大鼠肾脏IR模型.R组于夹闭双侧肾动脉前15 min至再灌注30 min静脉泵注瑞芬太尼1.0 μg·kg^-1·min^-1,S组和IR组静脉泵注等体积生理盐水.于缺血前15 min、再灌注3h、12 h和24 h时获取各组大鼠肾组织样本,采用流式细胞术检测肾组织细胞凋亡率,采用逆转录-聚合酶链反应（RT-PCR）法检测FasmRNA表达,采用免疫印迹法检测caspase-8和caspase-3激活量,光镜下以Paller法对大鼠肾小管损伤程度评分.结果 IR组肾小管损伤评分、细胞凋亡率、肾组织Fas mRNA表达及caspase-3激活量于再灌注3h升高、再灌注12h继续升高至再灌注24 h时达高峰（P＜0.01）,caspase-8激活量再灌注3h增高至再灌注12h达高峰、再灌注24h出现回落（P＜0.01）.与S组比较,IR组及R组再灌注3h、12h和24 h时肾小管损伤评分、细胞凋亡率、肾组织Fas mRNA表达、caspase-8激活量及再灌注12 h和24 h时caspase-3激活量均升高（P＜0.05或0.01）.与IR组比较,R组再灌注后3h、12h及24 h肾小管损伤评分、细胞凋亡率、肾组织Fas mRNA的表达、caspase-8及caspase-3激活量均降低（P＜0.05或0.01）.结论 瑞芬太尼通过减少Fas受体表达及降低caspase-8、caspase-3激活量调控Fas凋亡信号通路,从而抑制细胞凋亡,减轻大鼠肾脏IR损伤.
Objective To investigate the effects and mechanism of remifentanil on renal ischemia/reperfusion（IR） injury via mediating Fas apoptosis signal pathway in rats.Methods Sprague-Dawley rats were divided into 3 groups （n =20 each） by using the random number table method：sham operation group （S group）,IR control group （IR group）,experimental group （Rgroup）.The renal IR model was prepared by clamping the bilateral renal arteries for 45 min followedby reperfusion in IR group and R group.In R group,remifentanil was infused at 1.0μg·kg-1 ·min-1 via the tail vein starting from 15 min before ischemia until 30 min of reperfusion.In S group and IR group,the same volume of physiological saline was given.At 15 min before ischemia and at 3 h,12 h,24 h of reperfusion,the renal tissue samples were obtained for detecting the apoptosis rate by flow cytometry,determining the level of Fas mRNA expression by RT-PCR,the level of caspase-8 and caspase-3 activation by Western blotting,and scoring the number of kidney tubules injury by Paller＇method.Results In IR group,the renal tubular injury score,the apoptosis rate,the expression of Fas mRNA and the activation of caspase-3 in renal tissue increased at 3 h after reperfusion,and those continued to increase at 12 h after reperfusion and reached the peak at 24 h after reperfusion （P〈0.01）,and the activity of caspase-8 increased at 3 b,reached the peak at 12 h after reperfusion and decreased at 24 h after reperfusion （P〈0.01）.As compared with S group,the renal tubular injury score,apoptosis rate,the expression of Fas mRNA and the activation of caspase-3 at 3 h,12 h and 24 h of reperfusion and the activation of caspase-8 at 12 h,24 h of reperfusion were all increased in IR group and R group （P〈0.05 or 0.01）.As compared with IR group,the renal tubular injury score,apoptosis rate,the expression of Fas mRNA and the activation of caspase-8 and caspase-3 at 3 h,12 h and 24 h of reperfusion were decreased in R group （P〈0.05 or 0.01）.Conclusion Remi
作者
金小雪
牛竞辉
齐琪
刘博阳
吕艳霞
王秀丽
王秋筠
吴川
Jin Xiaoxue;Niu Jinghui;Qi Qi;Liu Boyang;Lv Yanxia;Wang Xiuli;Wang Qiujun;Wu Chuan(Department of Anesthesiology,Third Affiliated Hospital of Hebei Medical University,Shijiazhuang 050051,China)
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2018年第5期282-287,共6页
Chinese Journal of Organ Transplantation
基金
河北省科学技术研究与发展计划项目（10206133D）
