吡格列酮减轻脑缺血再灌注小鼠脑白质损伤  

Pioglitazone attenuates white matter injury in mice with cerebral ischemia-reperfusion

作　　者：王荣亮[1] 闫峰[1] 王艺霖 罗玉敏[1] 马舒贝 Wang Rongliang;Yan Feng;Wang Yilin;Luo Yumin;Ma Shubei(Institute of Cerebrovascular Disease,Xuanwu Hospital,Capital Medical University,Beijing 100000,China;Department of Neurology,the Affiliated Municipal Central Hospital,Dalian University of Technology,Dalian 116033,China)

机构地区：[1]首都医科大学附属宣武医院脑血管病研究室,北京100000 [2]大连理工大学附属中心医院神经内科,大连116033

出　　处：《国际脑血管病杂志》2022年第7期500-507,共8页International Journal of Cerebrovascular Diseases

基　　金：辽宁省自然科学基金指导项目(2019-ZD-0884);大连市医学科学研究计划项目(1911005)。

摘　　要：目的探讨吡格列酮对小鼠脑缺血再灌注后脑白质损伤的影响及其作用机制。方法 42只青年雄性C57BL/6J小鼠按随机数字表法分为假手术组、模型组和吡格列酮组, 每组14只。采用线栓法短暂性闭塞大脑中动脉制备脑缺血再灌注模型。模型制作后第3天和第7天采用贴条试验进行神经功能评估。模型制作后第7天处死小鼠, 应用HE染色检测脑梗死范围, 通过免疫荧光染色和免疫印迹分析检测脑白质损伤程度以及小胶质细胞表型变化。结果在脑缺血再灌注后第7天, 与模型组相比, PGZ组小鼠移除贴条时间显著缩短(P<0.05), 脑梗死体积百分比显著缩小(P<0.05), 皮质区和纹状体区MBP/NF200荧光强度比值显著增高(P均<0.05), CD16+/Iba1+小胶质细胞数量显著减少(P<0.01), 而CD206+/Iba1+小胶质细胞数量有增多的趋势, 但未达到统计学差异。结论吡格列酮可减轻脑缺血再灌注小鼠脑白质损伤程度和神经功能损伤, 其机制可能与调节小胶质细胞由M1型向M2型转化有关。Objective To investigate the effect of pioglitazone on white matter injury after cerebral ischemia-reperfusion in mice and its mechanism.Methods Forty-two young male C57BL/6J mice were randomly divided into sham operation group,model group,and pioglitazone group(n=14 in each group).The model of cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion with suture-occluded method.On the 3rd and 7th day after the establishment of the model,the neural function was assessed by the adhesive removal test.The mice were killed on the 7th day after the establishment of the model.HE staining was used to detect the extent of cerebral infarction.Immunofluorescence staining and Western blot analysis were used to detect the degree of white matter damage and the changes of microglia phenotype.Results On the 7th day after cerebral ischemia-reperfusion,the adhesive removal time in the PGZ group was significantly shortened compared with the model group(P<0.05),the percentage of cerebral infarction volume was significantly reduced(P<0.05),the ratio of MBP/NF200 fluorescence intensity in the cortical and striatal areas was significantly increased(all P<0.05),and the number of CD16+/Iba1+microglia was significantly decreased(P<0.01),while the number of CD206+/Iba1+microglia tended to increase,but there was no statistical difference.Conclusion Pioglitazone may reduce the degree of white matter injury and nerve function damage in mice with cerebral ischemia-reperfusion,and its mechanism may be associated with regulating the transformation of microglia from M1 type to M2 type.

关 键 词：脑缺血 再灌注损伤 吡格列酮 白质 神经保护药 疾病模型 动物 小鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]