治疗性高碳酸血症对局灶性脑缺血大鼠空间记忆功能的影响  

Effects of therapeutic hypercapnia on spatial memory after focal cerebral ischemia/reperfusion in rat

作　　者：赵萌 王天龙[1] 李文志[2] Zhao Meng;Wang Tianlong;Li Wenzhi(Department of Anesthesiology and Operating Theater,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院麻醉手术科,北京100053 [2]哈尔滨医科大学附属第二医院黑龙江省麻醉与危重病重点实验室

出　　处：《北京医学》2019年第4期287-291,共5页Beijing Medical Journal

摘　　要：目的探究治疗性高碳酸血症对局灶性脑缺血大鼠空间记忆功能的影响及其可能机制。方法选择体质量250～280 g的健康成年SD大鼠60只,随机分为3组,即假手术组(S组)、缺血再灌注组(I/R组)、治疗性高碳酸血症组(T组),每组20只。将大鼠麻醉后,采用左侧大脑中动脉栓塞法(middle cerebral artery occlusion, MCAO)制造大鼠局灶性脑缺血-再灌注(MCAO/reperfusion, MCAO/R)模型,栓塞2 h后进行再灌注。T组大鼠于再灌注的同时吸入外源性CO_22 h,使动脉血PaCO_2维持在80～100 mmHg(1 mmHg=0.133 kPa)。再灌注后的第7、14、21、28天对每组大鼠进行八臂迷宫测试,用苏木精-伊红(hematoxylin and esolin, HE)染色法观察再灌注24 h后各组大鼠海马组织细胞损伤情况,用蛋白质印迹技术(Western blotting)检测各组大鼠再灌注24 h后海马组织Bcl-2和Bax蛋白的表达水平。结果与I/R组相比,T组参考记忆错误(reference memory error, RME)明显减少,工作记忆错误(working memory error, WME)差异无统计学意义(P>0.05),所走距离较I/R组明显缩短。HE染色显示,与I/R组相比,T组海马组织神经细胞损伤明显减少。Western Blotting结果显示,T组大鼠海马区Bcl-2表达较I/R组明显升高,Bax表达水平较I/R组明显下降,差异均有统计学意义(P <0.05)。结论治疗性高碳酸血症(PaCO_2维持在80～100 mmHg)可以改善局灶性脑缺血大鼠的空间记忆功能,机制可能为保护脑组织,减少细胞凋亡。Objective To investigate the effects of therapeutic hypercapnia in focal cerebral ischemia in the rat middle cerebral artery occlusion(MCAO)model and the underlying mechanism.Methods Sixty adult male SD rats weighted 250-280 g were divided into three groups randomly:sham group(S group),ischemia-reperfusion group(I/R group)and therapeutic hypercapnia group(T group).The left middle cerebral artery was occluded for 2 h of MCAO in rats after anesthesia.T group rats inhaled carbon dioxide for 2 h during reperfusion to keep arterial blood PaCO2 within the ranges of 80-100 mmHg(1 mmHg=0.133 kPa).Spatial memory were evaluated with the 8-arm-maze on 7,14,21 and 28 days.The hippocampal histological damage and the percentage of apoptotic neurons were evaluated by hematoxylin and eosin(HE)staining as well as flow cytometry.Western blotting was used to investigate the changes of the apoptosis-related Bcl-2 and Bax proteins.Results The reference memory error(RME)of T group was lower than that of I/R group significantly(P<0.05);while for the working memory error(WME),there were no difference among the groups(P>0.05).The distance of T group was shorter than that of I/R group significantly(P<0.05).HE-stained showed that compared with the I/R group,hypercapnia treatment had a significantly protective effect from MCAO/R damage(P<0.05).Western blot showed that Bcl-2 levels were significantly increased and Bax levels were decrease!in the S group compared with the I/R group(P<0.05).Conclusions Therapenutic hypercapnia(keep arterial blood PaCO2 within the ranges of 80-100 mmHg)can improve spatial memory after focal cerebral ischemia in rats.Therapeutic hypercapnia promotes neurological functional recovery through antiapoptotic mechanisms.

关 键 词：治疗性高碳酸血症 局灶性脑缺血 空间记忆 

分 类 号：R743[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]