小续命汤对急性脑缺血再灌注损伤星形胶质细胞活化的影响  

Effect of Xiaoxuming Decoction on activation of astrocytes in acute cerebral ischemia/reperfusion injury

作　　者：付雪琴 王漫漫[1] 兰瑞[2] 张勇[3] 邹旭欢 王玮玮[1] 唐琛 刘双 李泓宇 FU Xue-qin;WANG Man-man;LAN Rui;ZHANG Yong;ZOU Xu-huan;WANG Wei-wei;TANG Chen;LIU Shuang;LI Hong-yu(Henan University of Chinese Medicine,Zhengzhou 450000,China;the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学,河南郑州450000 [2]河南中医药大学第一附属医院,河南郑州450000 [3]郑州大学第三附属医院,河南郑州450000

出　　处：《中国中药杂志》2023年第21期5830-5837,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81973618,81503422);河南省自然科学基金项目(202300410399);河南省中医药科学研究专项(2022JDZX090)。

摘　　要：探讨小续命汤对脑缺血再灌注损伤后星形胶质细胞活化的影响。采用大脑中动脉闭塞法建立脑缺血再灌注损伤模型,应用星形胶质细胞活化抑制剂氟代柠檬酸(FC)抑制星形胶质细胞活化。将大鼠随机分成假手术组、模型组、小续命汤组、小续命汤+FC组、小续命汤+Vehicle组,观察各组大鼠脑缺血再灌注24 h后的神经行为学变化和脑梗死情况,HE染色观察组织病理学变化,透射电镜观察星形胶质细胞亚显微结构,免疫荧光测定胶质纤维酸性蛋白(GFAP)、血小板反应蛋白1(TSP1)荧光强度,免疫印迹法测定脑组织GFAP、TSP1的表达。结果显示,模型组大鼠神经行为评分、脑梗死面积显著增加,小续命汤组、小续命汤+FC组和小续命汤+Vehicle组均可减轻大鼠神经行为学改变;模型组大鼠病理改变明显,小续命汤组、小续命汤+FC组和小续命汤+Vehicle组大鼠脑缺血再灌注损伤较轻;模型组大鼠星形胶质细胞亚显微结构肿胀明显,小续命汤组、小续命汤+FC组和小续命汤+Vehcile组可保护星形胶质细胞亚显微结构;模型组GFAP、TSP1荧光强度及蛋白表达量较假手术组表达增加,小续命汤组、小续命汤+FC组和小续命汤+Vehicle组均可下调GFAP、TSP1的表达,小续命汤与FC联用效果更明显。以上结果表明小续命汤可以改善脑缺血再灌注损伤,可能与通过抑制星形胶质细胞活化并下调GFAP、TSP1的表达有关。This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury.The model of cerebral IR injury was established using the middle cerebral artery occlusion method.Fluorocitrate(FC),an inhibitor of astrocyte activation,was applied to inhibit astrocyte activation.Rats were randomly divided into a sham group,a model group,a XXMD group,a XXMD+FC group,and a XXMD+Vehicle group.Neurobehavioral changes at 24 hours after cerebral IR injury,cerebral infarction,histopathological changes observed through HE staining,submicroscopic structure of astrocytes observed through transmission electron microscopy,fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence,and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group.The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group.The XXMD group,the XXMD+FC group,and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats.The pathological changes in the brain were evident in the model group,while the XXMD group,the XXMD+FC group,and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats.The submicroscopic structure of astrocytes in the model group showed significant swelling,whereas the XXMD group,the XXMD+FC group,and XXMD+Vehicle group protected the submicroscopic structure of astrocytes.The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group.However,the XXMD group,the XXMD+FC group,and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1.The combination of XXMD and FC showed a more pronounced effect.These results indicate that XXMD can improve cerebral IR injury,possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.

关 键 词：小续命汤 脑缺血再灌注 星形胶质细胞活化 胶质纤维酸性蛋白(GFAP) 血小板反应蛋白1(TSP1) 

分 类 号：R285.5[医药卫生—中药学]