VX-765对失血性休克复苏大鼠认知功能的影响  

Effect of VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation

作　　者：于红[1] 郑维朝 张冬雪[2] 白杨[1] 王旭鹏[1] 白晶 张立民[1] Yu Hong;Zheng Weichao;Zhang Dongxue;Bai Yang;Wang Xupeng;Bai Jing;Zhang Limin(Department of Anesthesiology,Cangzhou Central Hospital,Cangzhou 061000,China;Department of Gerontology,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院麻醉科,061000 [2]沧州市中心医院老年内科,061000

出　　处：《中华麻醉学杂志》2020年第2期229-232,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81701296)。

摘　　要：目的评价VX-765对失血性休克复苏大鼠认知功能的影响。方法清洁级健康雄性SD大鼠48只,9~10周龄,体重350~400 g。采用随机数字表法分为4组(n=12):假手术组(S组)、失血性休克复苏组(H组)、VX-765组(V组)和溶剂对照组(C组)。股静脉放血至MAP为25~35 mmHg并维持60 min,将收集的血液在15 min内回输体内达到初始血压水平进行复苏,必要时输注生理盐水,建立失血性休克复苏模型;V组和C组复苏结束后立即向股静脉注射VX-765 1 mg/kg或等量0.4%聚乙二醇(VX-765溶剂)。于复苏结束后12 h时每组随机取6只大鼠处死取大脑皮质,采用免疫荧光法确定神经元焦亡率,T2加权成像法检测皮质水肿程度,复苏后7 d时每组余6只大鼠采用旷场实验测定认知功能。结果与S组比较,H组、V组和C组复苏后12 h时皮质神经元焦亡率升高,水肿程度增加,复苏后7 d时大鼠中央格路程和直立次数减少,中央格停留时间缩短(P<0.05);与H组和C组比较,V组复苏后12 h时皮质神经元焦亡率降低,水肿程度降低,复苏后7 d时大鼠中央格路程和直立次数增加,中央格停留时间延长(P<0.05)。结论 VX-765可改善失血性休克复苏大鼠认知功能,其机制与抑制皮质神经元焦亡有关。Objective To evaluate the effect of selective inhibitor of caspase-1 VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation(HSR).Methods Forty-eight clean-grade healthy male Sprague-Dawley rats,aged 9-10 weeks,weighing 350-400 g,were divided into 4 groups(n=12 each)using a random number table method:sham operation group(S group),HSR group(H group),VX-765 group(V group),and solvent control group(C group).The rats in H,V and C groups were subjected to hemorrhage by bleeding from femoral vein to achieve mean arterial pressure of 25-35 mmHg which was maintained at this level for 60 min followed by resuscitation with shed blood within 15 min to restore blood pressure,and normal saline was infused when needed.VX-7651 mg/kg and 0.4%polyethylene glycol 1 mg/kg were intravenously injected via the femoral vein immediately after the end of resuscitation in V and C groups,respectively.Six rats in each group were selected and sacrificed at 12 h after the end of resuscitation,and the cerebral cortex was removed for determination of neuronal pyroptosis(by immunofluorescence)and degree of cortical edema(using T2-weighted imaging).Cognitive function was measured by open field test on day 7 after resuscitation in the rest 6 rats in each group.Results Compared with S group,the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly increased,the distance in the central square and the number of standing on the back legs were decreased on day 7 after resuscitation,and the time spent in the central square was shortened in H,V and C groups(P<0.05).Compared with H and C groups,the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly decreased,the distance in the central square and the number of standing on the back legs were increased on day 7 after resuscitation,and the time spent in the central square was prolonged in V group(P<0.05).Conclusion VX-765 can improve the cognitive function,and the m

关 键 词：半胱天冬酶抑制剂 休克 出血性 复苏术 大脑皮质 神经元 细胞焦亡 

分 类 号：R459.7[医药卫生—急诊医学]