MMP9介导血脑屏障破坏在偏头痛模型小鼠认知功能减退中的研究  

MMP9 mediated blood-brain barrier disruption in the pathogenesis of cognitive decline in migraine mice

作　　者：李维东 胡露宇 单争明 肖哲曼[1] Li Weidong;Hu Luyu;Shan Zhengming(Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区：[1]武汉大学人民医院神经内科,430060

出　　处：《卒中与神经疾病》2023年第6期583-588,共6页Stroke and Nervous Diseases

基　　金：国家自然科学基金资助项目(编号为81971055、81471133、82101292)。

摘　　要：目的 探讨基质金属蛋白酶9(Matrix metalloprotein 9,MMP9)参与偏头痛动物模型认知功能减退的机制。方法 使用炎性汤(Inflammatory soup, IS)建立偏头痛动物模型,用SB3CT(CAS:292605-14-2)来抑制mmp9表达,把C57BL/6小鼠分成假手术组(Sham组)、IS组和IS+SB3CT组,评估或检测各组行为学及血脑屏障完整性、MMP9水平和小胶质细胞增生情况。结果 应用炎性汤后偏头痛模型小鼠出现挠头次数增加,新物体识别能力降低;偏头痛模型小鼠脑内MMP9蛋白水平增高,荧光素钠渗透明显,出现了紧密连接蛋白降解,即血脑屏障破坏,并且在血管周围出现了小胶质细胞募集现象,而注射SB3CT能够逆转偏头痛模型小鼠的这些变化。结论 偏头痛模型小鼠脑内MMP9水平的增高降解了紧密连接蛋白Claudin5和Occludin,破坏血脑屏障的完整性,引起破坏区域小胶质细胞募集,这些可能与偏头痛模型小鼠的记忆力减退有关。Objective To investigate the mechanisms of matrix metalloproteinase 9(MMP9)involvement in cognitive decline in animal models of migraine.Methods Inflammatory soup(IS)was used to establish an animal model of migraine,and SB3CT(CAS:292605-14-2)was used to inhibit the expression of MMP9.C57BL/6 mice were randomly divided into sham,IS,and IS+SB3CT groups,and behavioral performance,blood-brain-barrier(BBB)integrity,MMP9 levels,and microglial cell proliferation were assessed or detected in each group.Results The IS group of migraine model mice showed increased head scratching and decreased recognition of new objects;increased MMP9 protein levels in the brains of migraine model mice;significant sodium fluorescein infiltration;degradation of tight junction proteins,i.e.,disruption of the integrity of the BBB;and microglia recruitment around the vasculature,whereas the injection of SB3CT was able to reverse these changes in migraine model mice.Conclusion The increased levels of MMP9 in the brains of migraine model mice degraded the tight junction proteins claudin5 and occludin,disrupted the integrity of the BBB,and induced microglia recruitment in the disrupted region,all of which may be related to memory decline in migraine model mice.

关 键 词：偏头痛 认知功能减退 基质金属蛋白酶9 血脑屏障 

分 类 号：R747.2[医药卫生—神经病学与精神病学]