亚低温对缺血性脑卒中小鼠血脑屏障损伤保护作用  

Protective effect of subhypothermia on blood‒brain barrier injury in mice with ischemic stroke

作　　者：钟超超 徐兴国[1] 苗海航 乔峤 秦毅彬[1] ZHONG Chaochao;XU Xingguo;MIAO Haihang;QIAO Qiao;QIN Yibin(Department of Anesthesiology,the Hospital Affiliated of Nantong University,Nantong,Jiangsu 226001,China)

机构地区：[1]南通大学附属医院麻醉科,江苏南通226001

出　　处：《安徽医药》2023年第2期337-340,共4页Anhui Medical and Pharmaceutical Journal

基　　金：南通市科技发展计划项目(MS12020026)。

摘　　要：目的探讨亚低温对缺血性脑卒中小鼠血脑屏障的保护作用,寻找亚低温发挥保护作用的机制。方法选取由南通大学实验动物中心提供的SPF级别雄性C57/BL6小鼠54只,分为假手术组(n=18)和卒中组(n=36),卒中组分为亚低温组(n=18)和常温组(n=18)。卒中组在行大脑中动脉阻塞手术后对亚低温组小鼠予以亚低温处理,在口腔温度监测下维持小鼠温度为(34±0.5)℃,其他组术后均置于保温毯上正常复温。术后每日对各组神经功能进行评分,同时使用错步时间检测卒中后小鼠行为运动功能。于术后第3天处死小鼠,取梗死脑区行蛋白质印迹法(Western blotting)检测血脑屏障黏附分子紧密连接蛋白(ZO-1),紧密连接跨膜蛋白(Claudin-5)的蛋白表达以判断血脑屏障损伤的程度。结果假手术组、亚低温组、常温组小鼠存活率分别为100%(18/18),94.44%(17/18),88.89%(16/18)。三组存活率比较,差异无统计学意义(χ^(2)=53.72,P=0.122)。卒中组小鼠术后第1、2、3天神经功能评分[(2.8±0.2)、(2.6±0.3)、(2.4±0.3)分]明显高于假手术组[(0.6±0.04)、(0.5±0.03)、(0.4±0.01)分],差异有统计学意义(t=2.94,P<0.001;t=2.86,P<0.001;t=2.98,P<0.001);卒中组中,常温组小鼠术后第1、2、3天神经功能评分均明显高于亚低温组[(2.0±0.3)、(1.9±0.2)、(1.8±0.2)分],差异有统计学意义。卒中组小鼠术后第1、2、3天前后肢的平均错步比例(26.8%_(前)、32%_(后);29.0%_(前)、31.1%_(后);31.8%_(前)、33.1%_(后))均高于假手术组(均为3%_(前)、3%_(后)),差异有统计学意义(χ^(2)=29.05,P=0.002;χ^(2)=28.76,P=0.003;χ^(2)=26.42,P=0.005),且常温组小鼠术后第1、2、3天前后肢平均错步的比例高于亚低温组(16.6%_(前)、16.9%_(后);18.6%_(前)、17.9%_(后);20.8%_(前)、19.9%_(后)),差异有统计学意义(χ^(2)=27.35,P=0.004;χ^(2)=26.59,P=0.004;χ^(2)=24.12,P=0.007)。存活的小鼠,脑卒中可以显著降低小鼠脑卒中脑组织中血脑屏障黏�Objective To investigate the protective effect of subhypothermia on blood‒brain barrier injury in mice with ischemic stroke,and to explore the mechanism of the protective effect of subhypothermia.Methods A total of 54 SPF-grade male C57/BL6 mice provided by the Experimental Animal Center of Nantong University were selected and divided into a sham-operated group(n=18)and a stroke group(n=36),and the stroke group was divided into a subhypothermia group(n=18)and a normothermic group(n=18).In the stroke group,mice in the subcritical group were treated with subcritical temperature after middle cerebral artery obstruction surgery,and the temperature of the mice was maintained at(34±0.5)℃ under oral temperature monitoring,while all other groups were placed on a thermal blanket for normal rewarming after surgery.The neurological function of each group was scored daily after surgery,and the poststroke behavioral-motor function of the mice was also measured using staggered time.The mice were sacrificed on the third day after surgery,and the protein expression of ZO-1 and Claudin-5 was measured by western blotting to determine the extent of blood‒brain barrier damage.Results The survival rates of the sham group,subhypothermia group and normothermic groups of mice were 100%(18/18),94.44%(17/18),and 88.89%(16/18),respectively.There was no significant difference in the survival rate among the three groups(χ^(2)=53.72,P=0.122).The neurological function scores on postoperative days 1,2,and 3 were significantly higher in the stroke group[(2.8±0.2),(2.6±0.3),(2.4±0.3)]than in the sham group[(0.6±0.04),(0.5±0.03),and(0.4±0.01)],with statistically significant differences(t=2.94,P<0.001;t=2.86,P<0.001;t=2.98,P<0.001).In the stroke group,the neurological function scores on postoperative days 1,2 and 3 were significantly higher in the normothermic group than in the subhypothermia group[(2.0±0.3),(1.9±0.2),and(1.8±0.2)],and the differences were statistically significant.In the stroke group,the average proportion of hind

关 键 词：低温 人工 脑梗死 缺血性脑卒中 血脑屏障 

分 类 号：R743.3[医药卫生—神经病学与精神病学]