黄芪甲苷基于血管内皮细胞间连接对脑缺血/再灌注大鼠脑保护作用  

Protective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury in Rats Based on Vascular Endothelial Junction

作　　者：杜澍金[1] 张冬[1] 张豪 张紫微[1] 周晓红[1] 高维娟[1] DU Shujin;ZHANG Dong;ZHANG Hao;ZHANG Ziwei;ZHOU Xiaohong;GAO Weijuan(Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease,Hebei University of Chinese Medicine,Shijiazhuang 050200,Hebei,China;Maternal and Child Care Service Centre,Shijiazhuang 050200,Hebei,China)

机构地区：[1]河北中医学院,河北省心脑血管病中医药防治研究重点实验室,河北石家庄050200 [2]石家庄鹿泉区妇幼保健院,河北石家庄050200

出　　处：《辽宁中医药大学学报》2021年第4期37-41,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：河北省自然科学基金面上项目(H2019423074);河北省中医药管理局科技计划项目(2018111);河北中医学院青年基金项目(2017001);河北中医学院优秀青年教师基础研究计划项目(YQ2019007);河北省研究生创新资助项目(CXZZBS2019156)。

摘　　要：目的探讨黄芪甲苷对脑缺血/再灌注损伤大鼠脑血管内皮间连接的保护作用及机制。方法选取健康清洁级、雄性、SD大鼠40只,随机分为假手术组(Sham组)、脑缺血/再灌注损伤模型组(I/R组)、模型+黄芪甲苷组(AST-IV组)。Sham组只分离、暴露颈部血管,不插线栓,其余各组大鼠以改良线栓法建立大脑中动脉阻塞/再灌注模型,缺血2 h,再灌注24 h。AST-IV组于再灌注的同时经腹腔注射黄芪甲苷(20 mg/kg)。ZEA LONGA评分法评价大鼠神经功能缺损情况;2,3,5-氯化三苯基四氮唑(TTC)染色检测脑梗死面积;HE染色观察脑组织病理改变;Western blot检测缺血侧脑组织血管内皮间连接蛋白β-链蛋白(β-catenin)和密封蛋白5(claudin-5)表达水平。结果与Sham组相比,I/R组大鼠神经功能缺损严重(P<0.05),脑梗死体积明显增加(P<0.05),脑组织病理改变明显,claudin-5和β-catenin表达下调(P<0.05)。与I/R组相比,AST-IV组大鼠神经功能损伤减轻(P<0.05),脑梗死体积减小(P<0.05),脑组织病理改变减轻,β-catenin和claudin-5表达增多(P<0.05)。结论黄芪甲苷可明显改善大鼠脑缺血/再灌注损伤,其作用可能与促进缺血区脑组织血管内皮间连接蛋白claudin-5和β-catenin的表达相关。Objective To investigate the protective effect and mechanism of astragaloside IV on cerebral vascular endothelial junction in rats with cerebral ischemia/reperfusion injury. Methods 40 healthy,clean,male SD rats were randomly divided into Sham group,cerebral ischemia/reperfusion group(I/R group)and astragaloside IV group(AST-IV group). Only vessels were isolated and exposed in the Sham group without ligation or insertion of wires,and the middle cerebral artery occlusion and reperfusion models were established in the other groups of rats by modified and threaded occlusion,ischemia for 2 h and reperfusion for 24 h. AST-IV group was injected intraperitoneally with astragaloside IV(20 mg/kg)at the same time of reperfusion. Zea Longa score was used to evaluate the neurological deficits in each group. The volume of cerebral infarction was detected by TTC staining. HE staining was used to observe the pathological changes of brain tissue. The protein expression levels of vascular endothelial β-catenin and claudin-5 were detected by Western blot. Results Compared with Sham group,rats in I/R group showed more serious neurological deficits(P<0.05),significantly increased cerebral infarction volume(P<0.05),significant pathological changes in brain tissue,and down-regulated expressions of claudin-5 and β-catenin(P<0.05). Compared with the I/R group,the AST-IV group showed reduced nerve function damage(P<0.05),decreased cerebral infarction volume(P<0.05),reduced pathological changes of brain tissue,and increased expressions of claudin-5 and β-catenin(P<0.05). Conclusion Astragaloside IV can significantly improve cerebral ischemia/reperfusion injury in rats,and its mechanism may be related to promoting the protein expression of endothelial junction,such as claudin-5 and β-catenin in ischemic brain tissue.

关 键 词：黄芪甲苷 脑缺血 再灌注 内皮间连接 

分 类 号：R743.31[医药卫生—神经病学与精神病学]