右美托咪定调控Apelin/APJ信号系统减轻小鼠脑出血损伤的机制研究  

STUDY ON MECHANISM OF DEXMEDETOMIDINE REGULATING APELIN/APJ SIGNAL SYSTEM TO REDUCE INTRACEREBRAL HEMORRHAGE INJURY IN MICE

作　　者：董晓柳[1] 董伟[2] 张秀清[1] 刘蔚然 高铭 司味鑫 宋丽华[1] 张利[2] DONG Xiaoliu;DONG Wei;ZHANG Xiuqing;LIU Weiran;GAO Ming;SI Weixin;SONG Lihua;ZHANG Li(Department of Neurorehabilitation,Tangshan People’s Hospital,Tangshan 063000,China)

机构地区：[1]河北省唐山市人民医院神经康复科,063000 [2]唐山市人民医院神经外科

出　　处：《中国煤炭工业医学杂志》2022年第3期225-230,共6页Chinese Journal of Coal Industry Medicine

基　　金：河北省医学科学研究课题计划项目(编号:20211512);唐山市人才资助项目(编号:A202110019)。

摘　　要：目的 通过研究右美托咪定(Dex)对脑出血(ICH)小鼠脑损伤后血管紧张素受体AT1相关受体蛋白(Apelin)/孤儿G蛋白偶联受体(APJ)信号系统的影响,探究其在脑出血后减轻脑损伤的可能作用机制。方法选取健康雄性C57BL/6J小鼠120只,应用胶原酶法制作小鼠ICH模型,采用随机数字表法将小鼠分为三组:假手术组(sham组)、脑出血组(ICH组)、脑出血+右美托咪定组(ICH+Dex组),每组40只。ICH+Dex组于造模成功后,30min内通过腹腔注射右美托咪定[25μg/(kg·d)],连续给药3天,sham组和ICH组于相应时间点给予等量的生理盐水。在ICH第1、3天分别进行神经功能损伤评分(mNSS score)以评价小鼠神经功能障碍;在ICH第3天,利用干湿重法评估脑水肿程度、通过蛋白印迹分析测定脑组织紧密连接蛋白ZO-1及claudin-5的表达水平、采用ELISA法测定脑组织Apelin及APJ的表达变化、采用TUNEL法检测神经元凋亡情况。结果 与sham组比较,ICH组小鼠神经功能评分、脑组织含水量、神经元凋亡数均升高(P<0.05),而ZO-1、claudin-5及Apelin、APJ表达降低(P<0.05);与ICH组相比,ICH+Dex组小鼠神经功能评分及脑组织含水量及神经元凋亡细胞数均降低(P<0.05),而ZO-1、claudin-5及Apelin、APJ表达升高(P<0.05)。结论 右美托咪定对脑出血小鼠具有脑保护作用,该作用可能是通过调控Apelin/APJ信号系统从而保护血脑屏障完整性,减轻脑水肿、减少神经元细胞凋亡,从而改善神经功能障碍。Objective Effect of Dexmedetomidine(Dex) on angiotensin receptor AT1-related receptor protein(Apelin)/orphan G protein-coupled receptor(APJ) signal system after brain injury in mice with intracerebral hemorrhage(ICH),and explore its possible mechanism of alleviating brain injury.Methods One hundred and twenty male C57 BL/6 J mice were selected,and the model of intracerebral hemorrhage was made by collagenase method.They were randomly divided into three groups by random number table method:sham operation group(sham group),ICH group(ICH group) and ICH+Dexmedetomidine group(ICH+Dex group),with 40 mice in each group.In the ICH+Dex group,dexmedetomidine [25 μg/(kg·d)] was injected intraperitoneally within 30 minutes after successful modeling,and the drug was given continuously for three days,while sham group and ICH group were given the same amount of normal saline at corresponding time points.Neurological impairment score(mNSS score) was performed on the day 1 and day 3 after ICH to evaluate neurological dysfunction in mice.On the day 3 after ICH,the brain tissue was weighed to assess the degree ofbrain edema,the tight junction protein ZO-1 and occlaudin-5 were determined by western blot and the expression changes of Apelin and APJ in brain tissue were determined by ELISA and TUNEL method to detect neuronal apoptosis.Results Compared with the sham group,the neurological function score,brain water content,and neuronal apoptosis of the ICH group increased(P<0.05),while the expressions of ZO-1,claudin-5,Apelin and APJ decreased(P<0.05).Compared with the ICH group,the neurological function score,brain tissue water content and the number of neuronal apoptotic cells in the ICH+Dex group decreased(P<0.05),while the expression of ZO-1,claudin-5,Apelin and APJ increased(P<0.05).Conclusion Dexmedetomidine has a protective effect on mice with cerebral hemorrhage,which may be through regulating the Apelin/APJ signal system to protect the integrity of the blood-brain barrier,reduce brain edema,reduce neuronal cell apoptosis,and

关 键 词：右美托咪定 脑出血 脑损伤 Apelin/APJ信号系统 

分 类 号：R743.34[医药卫生—神经病学与精神病学]