银杏叶提取物对急性脑梗死模型大鼠血脑屏障功能及PI3K/AKT信号通路的影响及作用机制  

Effects and mechanism of Ginkgo biloba extract on blood-brain barrier function and PI3K/AKT signaling pathway in model rats with acute cerebral infarction

作　　者：谢涛波 钟纯正 符尧天 王国卿 米东华[4] XIE Tao-Bo;ZHONG Chun-Zheng;FU Yao-Tian(Department of Neurology,Danzhou People's Hospital of Hainan Province,Danzhou 571799,Hainan,China)

机构地区：[1]儋州市人民医院神经内科,海南儋州571799 [2]儋州市农垦医院神经内科 [3]儋州市人民医院精神病科 [4]首都医科大学附属北京天坛医院神经重症医学科

出　　处：《中国老年学杂志》2021年第20期4467-4471,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金条例项目(81601015)。

摘　　要：目的探究银杏叶提取物对急性脑梗死模型大鼠血脑屏障功能及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路的影响及作用机制。方法取60只SD大鼠随机分为假手术组、模型组、银杏叶提取物组(低剂量组和高剂量组),除假手术组外,其他组采用中动脉闭塞法复制急性脑梗死模型,银杏叶提取物组分别给予50 mg/kg、100 mg/kg的银杏叶提取物灌胃处理,连续灌胃7 d。采用伊文思蓝法检测脑组织渗透量,评价各组大鼠神经功能,测定脑水含量,TTC染色法测定脑组织梗死体积,TUNEL染色检测脑组织细胞凋亡,蛋白质印迹检测紧密连接相关蛋白(claudin-5、occludin)、切割后半胱氨酸天冬氨酸酶(cleaved caspase)-3和cleaved caspase-9、PI3K/AKT信号通路的表达,酶联免疫吸附试验(ELISA)检测炎症因子白细胞介素(IL)-6、IL-1β及肿瘤坏死因子(TNF)-α。结果与模型组比较,银杏叶提取物组神经损伤评分、脑组织含水量、脑梗死体积、脑组织中伊文思蓝含量、脑组织细胞凋亡率、cleaved caspase-3、cleaved caspase-9表达、脑组织匀浆液中IL-6、IL-1β及TNF-α含量明显降低,脑组织中claudin-5和occludin表达、p-PI3K/PI3K和p-AKT/AKT水平明显增加(P<0.05),以高剂量组改善显著(P<0.05)。结论银杏叶提取物可改善急性脑梗死模型大鼠神经功能,保护血脑屏障功能,可能与抑制脑组织细胞凋亡、减轻脑内炎症反应、活化PI3K/AKT信号通路有关。Objective To explore the effects and mechanism of Ginkgo biloba extract(GBE)on blood-brain barrier function and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway in model rats with acute cerebral infarction(ACI).Methods Sixty SD rats were enrolled and randomly divided into sham group,model group and GBE group(low-dose group and high-dose group).Except for sham group,ACI models were replicated in the other groups by middle artery occlusion.Low-dose and high-dose GBE group was intragastrically administered with 50 mg/kg and 100 mg/kg GBE for 7 d,respectively.The permeation of brain tissue was detected by Evans blue method.The nerve function in each group was evaluated,and content of brain water was measured.The infarction volume of brain tissues was detected by TTC staining.The apoptosis of brain tissue cells was detected by TUNEL staining.The expression of tight junction-related proteins(claudin-5,occludin),cysteine aspartase(cleaved caspase-3,cleaved caspase-9)and PI3K/AKT signaling pathway was detected by Western blot.The inflammatory factors interleukin(IL)-6,IL-1β,tumor necrosis factorα(TNF-α)were detected by ELISA.Results Compared with model group,score of nerve damage,water content of brain tissue,cerebral infarction volume,Evans blue content in brain tissue,apoptosis rate of brain tissue cells,expression of cleaved caspase-3 and cleaved caspase-9,contents of IL-6,IL-1βand TNF-αin brain homogenate were significantly decreased in GBE group,while expression of claudin-5 and occludin in brain tissue,levels of p-PI3K/PI3K and p-AKT/AKT were significantly increased(P<0.05).And the improvement was more significant in high-dose group(P<0.05).Conclusions GBE could improve the nerve function of ACI rats,and protect blood-brain barrier function,which might be related to inhibiting apoptosis of brain tissue cells,alleviating inflammation response in the brain and activating PI3K/AKT signaling pathway.

关 键 词：银杏叶提取物 急性脑梗死 血脑屏障功能 PI3K/AKT信号通路 

分 类 号：R285.5[医药卫生—中药学]