右美托咪定通过提高GDNF释放发挥抗缺血性卒中损伤作用  

Dexmedetomidine plays an anti-ischemic stroke role by increasing the release of GDNF

作　　者：杨海燕[1] 马晓梅 吴芳[1] 王慧[1] Yang Haiyan;Ma Xiaomei;Wu Fang;Wang Hui(Dept of Anesthesiology and Perioperative Medicine,General Hospital of Ningxia Medical University,Yinchuan 750004)

机构地区：[1]宁夏医科大学总医院麻醉与围术期医学科,银川750004

出　　处：《安徽医科大学学报》2024年第10期1729-1736,共8页Acta Universitatis Medicinalis Anhui

基　　金：宁夏自然科学基金项目(编号:2021AAC03331)。

摘　　要：目的探究右美托咪定(Dex)发挥抗缺血性卒中作用时对胶质细胞源性神经营养因子(GDNF)释放的影响。方法将SD大鼠随机分为假手术组(Sham组),假手术+右美托咪定组(Sham+Dex组),缺血性卒中组(IS组),缺血性卒中+右美托咪定组(IS+Dex组),缺血性卒中+右美托咪定组+anti-GDNF(IS+Dex+anti-GDNF组),每组15只。采用Longa线栓法构建IS模型,24 h后各组取大鼠开展神经功能评分,将大鼠处死,取脑脊液和外周血检测GDNF含量,取全脑进行氯化三苯基四氮唑(TTC)染色评估脑缺血梗死区域面积,取全脑组织包埋、切片,通过免疫荧光检测星形胶质细胞活化,取缺血核心区组织通过qRT-PCR检测星形胶质细胞活化表型。结果与Sham组相比,Sham+Dex组各项指标没有明显变化,IS组大鼠神经功能评分增加(P<0.05),出现了明显的局部梗死区域,外周与中枢系统中GDNF释放增加(P<0.05),且IS造成小胶质细胞活化,神经毒性和神经保护性表型基因表达都明显升高(P<0.05);与IS组相比,IS+Dex组大鼠神经功能评分明显减少(P<0.05),局部梗死区域面积明显降低(P<0.05),且GDNF释放进一步增加(P<0.05),神经毒性星形胶质细胞表型基因表达明显减少(P<0.05),而神经保护性星形胶质细胞表型基因表达进一步升高(P<0.05)。然而,与IS+Dex组相比,anti-GDNF抗体的干预明显逆转了Dex的治疗作用。结论Dex通过抑制神经毒性星形胶质细胞表型,提高神经保护性星形胶质细胞表型占比,进一步促进GDNF释放,发挥抗IS作用。Objective To investigate the effect of dexmedetomidine(Dex)on the release of glial cell line-derived neurotrophic factor(GDNF)during the anti-ischemic stroke.Methods SD rats were randomly divided into sham group(Sham group),sham+dexmedetomidine group(Sham+Dex group),ischemic stroke group(IS group),ischemic stroke+dexmedetomidine group(IS+Dex group),ischemic stroke+dexmedetomidine group+anti-GDNF(IS+Dex+anti-GDNF group),with 15 rats in each group.IS model was established by Longa′s methods.24 hours later,the neurological scores were evaluated.Then,the rats were sacrificed and the cerebral spinal fluid,as well as the peripheral blood,were collected to detect the content of GDNF.In addition,TTC staining was used to evaluate the area of cerebral ischemic infarction,and immunofluorescence was applied to detect the activation of astrocytes.Furthermore,the activation phenotype of astrocytes was detected by qRT-PCR.Results Compared with Sham group,there were no significant changes in all indexes of rats in Sham+Dex group.In IS group,the neurological score increased(P<0.05),the local infarction area appeared,the release of GDNF in peripheral and central system increased(P<0.05),and the microglia activation was induced by IS,and the expression of neurotoxic and neuroprotective phenotype genes increased significantly(P<0.05).Compared with the IS group,the neurological function score of the rats in the IS+Dex group significantly decreased(P<0.05),the local infarct area was significantly reduced(P<0.05),and the release of GDNF further increased(P<0.05).The expression of neurotoxic astrocyte phenotype genes significantly decreased(P<0.05),while the expression of neuroprotective astrocyte phenotype genes further increased(P<0.05).However,intervention with anti-GDNF antibody obviously reversed the therapeutic effect of Dex compared with the IS+Dex group.Conclusion Dex can inhibit the phenotype of neurotoxic astrocytes,increase the proportion of neuroprotective astrocytes,further promote the release of GDNF,and play an anti-isc

关 键 词：右美托咪定 星形胶质细胞 极化 GDNF 缺血性卒中 

分 类 号：R743.33[医药卫生—神经病学与精神病学]