脑心清对脑缺血再灌注损伤模型大鼠的保护机制  

Protective mechanism of Naoxinqing Capsule in rat models of cerebral ischemia/reperfusion injury

作　　者：闵冬雨[1] 李红岩 关乐[1] 常江 张海宁[4] 崔馨月 王鹏[6] 曹永刚[6] Min Dongyu;Li Hongyan;Guan Le;Chang Jiang;Zhang Haining;Cui Xinyue;Wang Peng;Cao Yonggang(the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Shenyang Madison Technology Co.,Ltd.,Shenyang 110066,Liaoning Province,China;Food and Drug Inspection and Testing Center of Huludao,Huludao 125000,Liaoning Province,China;Shenyang Food and Drug Administration,Shenyang 110001,Liaoning Province,China;Class One,Department of Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning Province,China;Functional Laboratory of Harbin Medical University(Daqing),Daqing 163319,Heilongjiang Province,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁省沈阳市110032 [2]沈阳麦迪信科技有限公司,辽宁省沈阳市110066 [3]葫芦岛市食品药品检验检测中心,辽宁省葫芦岛市125000 [4]沈阳市食品药品监督管理局,辽宁省沈阳市110001 [5]辽宁中医药大学,辽宁省沈阳市110847 [6]哈尔滨医科大学大庆校区机能实验室,黑龙江省大庆市163319

出　　处：《中国组织工程研究》2020年第2期215-222,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家重点基础研究发展计划(973计划)项目(2013CB531704);辽宁中医药大学中医脏象理论及应用国家教育部重点实验室开放基金(zyzx1705),项目负责人:闵冬雨;辽宁省科技厅项目(20180551110)~~

摘　　要：背景:脑心清胶囊用于脑缺血再灌注损伤的治疗由来已久,然而针对其作用机制的深入研究则相对较少。目的:应用分子生物学手段考察脑心清胶囊对脑缺血再灌注损伤沙鼠模型的治疗作用。方法:实验方案经辽宁中医药大学动物实验伦理委员会批准(批准号为21000092017072)。将80只雄性蒙古沙鼠随机分为假手术组、模型组、脑心清组及脑络通组,后3组沙鼠应用无创微动脉夹同时夹闭双侧颈总动脉5 min后松开,建立脑缺血再灌注损伤模型;假手术组不夹闭双侧颈总动脉。术后次日开始假手术组正常饲养,模型组灌服同体积的生理盐水,脑心清组按照100 mg/(kg?d)灌胃给药,脑络通组按照100 mg/(kg?d)灌胃给药,连续给药21 d。在实验结束前1周进行水迷宫实验,实验结束后麻醉下处死沙鼠取脑组织。检测沙鼠的学习记忆功能、海马神经元、脑血管及对应的分子变化情况。结果与结论:①同假手术组相比,模型组沙鼠学习能力显著下降。而脑心清组及脑络通组则可有效提升术后的学习能力下降趋势;②与模型组相比,脑心清组及脑络通组神经元显著增多,且排列较为整齐,细胞轮廓清晰,结构完整;③与模型组相比,脑心清组及脑络通组沙鼠的超氧化物歧化酶和乳酸脱氢酶活性,谷胱甘肽含量显著升高,丙二醛含量显著降低(P<0.01);④与模型组相比,脑心清组及脑络通组沙鼠海马组织ASC、NLRP3和Caspase-1蛋白表达下调(P<0.05);⑤与模型组相比,脑心清组及脑络通组沙鼠的白细胞介素18和白细胞介素1β含量明显降低(P<0.01);⑥与模型组相比,脑心清组及脑络通组沙鼠的血小板内皮细胞黏附分子1阳性细胞明显增多,细胞间连接紧密;⑦与模型组相比,脑心清组及脑络通组沙鼠海马组织血小板内皮细胞黏附分子1和磷酸化内皮型一氧化氮合酶表达显著上调,一氧化氮含量显著升高(P<0.01);⑧结果说明,脑心BACKGROUND:Naoxinqing capsule has been used for treating cerebral ischemia/reperfusion injury for a long time.However,there are relatively few in-depth studies on its mechanism.OBJECTIVE:To investigate the therapeutic effect of Naoxinqing Capsule on gerbil model of cerebral ischemia/reperfusion injury by molecular biological means.METHODS:The study was approved by the Laboratory Animal Ethical Committee of Liaoning University of Chinese Medicine,approval No.21000092017072.Eighty male Mongolian gerbils were randomly divided into sham,model,Naoxinqing and Naoluotong groups,and the latter three groups underwent bilateral common carotid artery clip for 5 minutes,to establish the model of cerebral ischemia/reperfusion injury.The sham group received no common carotid artery clip.Next day,the sham group fed normally,the model group was given normal saline,Naoxinqing group was given the 100 mg/(kg?d)Naoxinqing via gavage,and Naoluotong group given 100 mg/(kg?d)Naoluotong via gavage,respectively,for 21 consecutive days.The water maze test was conducted at 1 week before experiment ended.The brain tissue was removed after experiment.The learning and memory function,hippocampal neurons,cerebrovascular and corresponding molecular changes were detected.RESULTS AND CONCLUSION:(1)Compared with the sham group,the learning ability in the model group was decreased significantly.Naoxinqing and Naoluotong groups could effectively improve the learning ability after surgery.(2)Compared with the model group,the numbers of neurons in the Naoxinqing and Naoluotong groups were increased significantly,arranged regularly with clear contour and complete structure.(3)Compared with the model group,in the Naoxinqing and Naoluotong groups,the activities of superoxide dismutase and lactate dehydrogenase,and glutathione content were significantly increased,and the content of malonaldehyde was significantly decreased(P<0.01).(4)The expression levels of ASC,NLRP3 and Caspase-1 in the hippocampus in the Naoxinqing and Naoluotong groups were significan

关 键 词：脑心清胶囊 脑缺血再灌注 氧化应激 炎症 脑血管功能 细胞焦亡 

分 类 号：R452[医药卫生—治疗学] R453[医药卫生—临床医学]