出 处:《中华麻醉学杂志》2019年第9期1071-1075,共5页Chinese Journal of Anesthesiology
摘 要:目的评价鸢尾素预处理对大鼠全脑缺血再灌注损伤的影响。方法健康雄性SD大鼠36只,8~10周龄,体重250~300 g,采用随机数字表法,将其分为3组(n=12):假手术组(S组)、全脑缺血再灌注组(I/R组)和鸢尾素预处理组(I组)。采用夹闭双侧颈总动脉联合低血压(MAP 35~45 mmHg)的方法,建立大鼠全脑缺血再灌注损伤模型。缺血前30 min时I组静脉注射鸢尾素10μg/kg(用生理盐水稀释至10 ml);S组和I/R组静脉注射等容量生理盐水。再灌注3 d时进行Morris水迷宫实验评价大鼠认知功能。水迷宫实验结束后处死大鼠,取脑组织,HE染色法观察海马CA1区病理学结果,计算神经细胞坏死率;TUNEL染色法检测海马CA1区神经细胞凋亡情况,计算神经细胞凋亡率;分别采用免疫组化法和Western blot法测定海马CA1区胶质纤维酸性蛋白(GFAP)的表达;采用比色法检测海马组织髓过氧化物酶(MPO)活性,ELISA法检测海马组织TNF-α和IL-1β含量。结果与S组比较,I/R组第1~5天、I组第1~3天逃避潜伏期延长,I/R组和I组第1象限停留时间缩短,海马CA1区神经细胞坏死率和凋亡率升高,GFAP表达上调,海马组织MPO活性、TNF-α和IL-1β含量升高(P<0.05或0.01);与I/R组比较,I组第1~5天逃避潜伏期缩短,第1象限停留时间延长,海马CA1区神经细胞坏死率和凋亡率降低,GFAP表达下调,海马组织MPO活性、TNF-α和IL-1β含量降低(P<0.05或0.01)。结论鸢尾素预处理可减轻大鼠全脑缺血再灌注损伤,其机制可能与抑制海马星形胶质细胞激活,减轻炎症反应有关。Objective To evaluate the effect of irisin preconditioning on global cerebral ischemia-reperfusion(I/R)injury in rats.Methods Thirty-six healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-300 g,were divided into 3 groups(n=12 each)using a random number table method:sham operation group(group S),global cerebral I/R group(group I/R)and irisin preconditioning group(group I).Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension(MAP maintained at 35-45 mmHg)in anesthetized rats.At 30 min before ischemia,irisin 10μg/kg(diluted to 10μg/ml in normal saline)was intravenously injected in group I,and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test,and brains were removed for determination of histopathologic changes in hippocampal CA1 region(using HE staining),neuronal apoptosis in hippocampal CA1 region(Tunel staining),glial fibrillary acidic protein(GFAP)expression(by Western blot),myeloperoxidase(MPO)activity in the hippocampal tissues(by colorimetric assay),and contents of tumor necrosis factor-alpha(TNF-α)and interleukin-1beta(IL-1β)in hippocampal tissues(by enzyme-linked immunosorbent assay).The cell necrosis rate and apoptotic rate were calculated.Results Compared with group S,the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I,the time of staying at 1st quadrant was significantly shortened,the cell necrosis rate and apoptotic rate were increased,the expression of GFAP was up-regulated,and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups(P<0.05 or 0.01).Compared with group I/R,the escape latency was significantly shortened on 1-5 days,the time of staying at 1st quadrant was prolonged,the cell necrosis rate and apoptotic rate were decreased,the expression of GFAP was down-regulated
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