通心络胶囊对大鼠低压低氧暴露后炎症反应和脑组织水肿及认知功能的影响  

Effects of tongxinluo capsule on hippocampal inflammation,brain edema,and cognitive function of rats exposed to acute hypobaric hypoxia

作　　者：刘鹏飞[1] 胡艳婷 姜静雯 赵晟[1] 邓会 薛新颖[1] 潘磊[1] 崔磊[1] 王勇 乔辉[1] 李天佐[1] 赵斌江[1] LIU Pengfei;HU Yanting;JIANG Jingwen;ZHAO Sheng;DENG Hui;XUE Xinying;PAN Lei;CUI Lei;WANG Yong;QIAO Hui;LI Tianzuo;ZHAO Binjiang(Beijing Shijitan Hospital,Capital Medical University,Beijing 100038;China.2.Beijing Emergency Center,Beijing 100038)

机构地区：[1]首都医科大学附属北京世纪坛医院,北京100038 [2]北京急救中心,北京100038

出　　处：《中国比较医学杂志》2021年第6期69-76,共8页Chinese Journal of Comparative Medicine

基　　金：北京市中医药科技专项科研资助项目(JJ2016-85)。

摘　　要：目的探讨通心络胶囊对急性低压缺氧暴露大鼠认知功能损伤的神经保护作用及其相关机制。方法64只雄性Sprague-Dawley大鼠随机均分为四组,包括正常组(C),通心络组(TXL),低压低氧组(HH),和低压低氧+通心络组(TXL+HH)。在低压低氧暴露前,所有大鼠进行5 d水迷宫训练。然后在低压低氧环境下暴露7 d。7 d后,采用旷场实验,水迷宫实验测定认知功能,然后处死取海马组织,Western blot检测海马组织TLR-4、MyD88、IκB-α,NF-κB p65,AQP4,MMP-9的表达,ELISA检测血清和海马组织中IL-1β、TNF-α、IL-6的水平,HE染色观察海马组织病理学变化,并测定大鼠的脑水含量。结果(1)行为学实验:四组大鼠旷场实验结果无统计学差异(P>0.05);但在水迷宫空间探索实验中发现,与C组比较,HH组大鼠原平台所在象限停留时间及穿越平台次数明显降低(P<0.05);TXL干预后,大鼠原平台所在象限停留时间及穿越平台次数较低压低氧组明显升高,(P<0.05);(2)炎症指标比较:与C组比较,HH组大鼠血清及海马组织IL-1β、TNF-α、IL-6水平,海马TLR-4、MyD88、NF-κB p65蛋白水平明显升高(P<0.05),TXL干预后,炎症指标相关蛋白水平均下降(P<0.05);(3)海马组织损伤比较:HH组大鼠海马AQP4及MMP-9表达及脑水含量明显高于C组(P<0.05),海马区细胞排列紊乱,肿胀明显,边界模糊;而TXL干预后,AQP4,MMP-9表达及脑水含量均明显下降(P<0.05)。结论急性低压缺氧暴露可导致认知功能障碍和脑组织水肿,通心络干预可通过抑制TLR4/MyD88/NF-κB信号通路活化,减轻海马炎症,改善认知损伤和脑组织水肿。Objective To investigate the neuroprotective effect of tongxinluo capsule on cognitive impairment of rats exposed to acute hypobaric hypoxia and its related mechanism.Methods Sixty-four male Sprague-Dawley rats were randomly divided into four groups:the control group,tongxinluo group(TXL group),hypobaric hypoxia group(HH group),and tongxinluo+hypobaric hypoxia group(TXL+HH group).All rats were trained in a Morris water maze(MWM)for 5 days prior to hypobaric hypoxia exposure.They were then exposed to hypobaric hypoxia for 7 days.After 7 days,the rats’cognitive function was evaluated by open field and MWM tests.The hippocampi were then extracted for molecular biological examination.Morphological changes were observed by pathological staining.The expressions of TLR-4,MyD88,IκBα,NF-κB p65,and AQP4 in the hippocampus were detected by Western blot.Results In the behavioral experiment,no significant difference in the open field test was observed among the four groups(P>0.05).Likewise,in the training part of the MWM tests,no significant difference in the escape latency was found among the four groups(P>0.05).However,in the probe trials,the residence time in the targeted quadrant and the crossing time to the original platform were significantly shorter in the rats exposed to hypobaric hypoxia than in the control group(P<0.05).Tongxinluo treatment significantly attenuated hypobaric hypoxia-induced cognitive impairment(P<0.05).Next,measurement of inflammatory markers showed that the serum and hippocampal IL-1β,TNF-α,and IL-6 levels as well as the hippocampal TLR-4,MyD88,and NF-κB p65 protein levels were all significantly higher in the HH group than in the control group(P<0.05).The levels of these inflammatory proteins decreased after TXL intervention(P<0.05).Finally,examination of hippocampal tissue damage revealed that hypobaric hypoxia increased the brain water content,with increased AQP4 and MMP-9 expression in the hippocampus(P<0.05).The cells in the hippocampus were disordered with obvious swelling and blurred

关 键 词：通心络 低压低氧 认知障碍 脑水肿 炎症 TLR4 

分 类 号：R-33[医药卫生]