大气细颗粒物PM2．5诱导自噬激活加重大鼠脑缺血损伤  

Atmospheric fine particulate matter PM2.5 aggravated cerebral ischemic injury by autophagy activation

作　　者：高丽[1] 李杨 王飞[1] 王永刚[3] GAO Li;LI Yang;WANG Fei(Department of Neurology,South Campus,Ren di Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 201100,China)

机构地区：[1]上海交通大学医学院附属仁济医院南院神经内科,201100 [2]上海交通大学医学院南院附属仁济医院放射科,201100 [3]上海交通大学医学院附属仁济医院东院神经内科

出　　处：《临床神经病学杂志》2018年第5期354-358,共5页Journal of Clinical Neurology

基　　金：上海市卫生和计划生育委员会科研课题青年项目(20164Y0077);上海交通大学医学院附属仁济医院种子基金培养计划(RJZZ14-018);上海交通大学医学院附属仁济医院南院国自然培育项目(2017PYQA04)

摘　　要：目的探讨大气细颗粒物PM2. 5暴露对大鼠脑缺血后梗死体积、行为学特征及脑内自噬激活的影响,为阐明PM2. 5加重脑缺血损伤的机制提供实验依据。方法采用16周龄有卒中倾向的自发高血压大鼠模型,随机分为5组,第1组为假手术组(Sham组),吸入新鲜过滤空气;第2组为对照组,吸入新鲜过滤的空气并予局灶性脑缺血模型(MCAO)手术处理;其余3组分别实施0. 1 mg/m3、1 mg/m3及10 mg/m3三种不同浓度的PM2. 5动态吸入染毒(0. 1 mg/m3PM2. 5染毒组、1 mg/m3PM2. 5染毒组及10 mg/m3PM2. 5染毒组)并予MCAO手术处理。参照zea-Longa评分法进行各组大鼠神经功能缺损评分,采用TTC染色法测定大鼠脑梗死体积,Western blotting法检测自噬相关蛋白LC3、Beclin 1的表达,并通过免疫荧光染色法检测各组大鼠脑内LC3、Beclin 1阳性细胞的分布。结果 Sham组大鼠未见脑梗死病灶,神经功能缺损评分为0分。与对照组及0. 1mg/m3PM2. 5染毒组比较,1 mg/m3及10 mg/m3PM2. 5染毒组大鼠脑梗体积明显增加,神经功能缺损评分明显增高(均P <0. 05)。与Sham组比较,对照组及1 mg/m3PM2. 5染毒组大鼠脑内LC3、Beclin 1的表达水平均明显上升(均P <0. 05)。与对照组比较,1 mg/m3PM2. 5染毒组大鼠脑内LC3、Beclin 1表达水平明显上升(均P <0. 05)。结论 PM2. 5暴露可增加自发高血压大鼠脑梗死体积,促进大鼠脑缺血后自噬的进一步激活,加重神经功能损伤。Objective To observe the effects of atmospheric fine paniculate matter PM2.5 exposure on cerebral infarction volume, behavioral characteristics and autophagy activation after cerebral ischemia in rats, and to provide experimental basis fur elucidating the mechanism of PM2.5 aggravating cerebral ischemic injury. Methods Sixteen- week-old male stroke prone spontaneously hypertensive rats were adopted in this study and were divided into five groups. The first group was the Sham group and pumped into filtered air. The second group was the control group, which was induced with middle cerebral artery occlusion （MCAO） after filtered air exposure. The other three groups were induced with MCAO after exposed with different continuous concentration of 0.1mg/m3 （0. 1 mg/m3 PM2.5 group）, 1 rag/m3（1 mg/m3 PM2.5 group） and 10 mg/m3 PM2.5 （10 mg/m3 PM2.5 group）, respectively. The neurological deficit was scored by zea-Longa score method. The infarct volume was measured by TTC stain in different groups. The expressions of autophagy related proteins LC3 and Beclin 1 were detected by Western blotting. The expression and distribution of LC3 and Beclin I fluorescent cells in brains were detected by immunofluorescence assay. Results There was no cerebral infarction in rats of Sham group, and the neurological defect score was zero. Compared with control group and 0.1 mg/m3 PM2.5 group, the infarct volumes and neurological deficit scores of 1 mg/m3 PM2.5 group and 10 mg/m3 PM2.5 group were significantly increased （all P 〈 0. 05）. Compared with Sham group, the expressions of LC3 and Beclin 1 in control group and 1 mg/m3 PM2.5 group were significantly increased （all P 〈0. 05）. Compared with control group, the expressions of LC3 and Beclin 1 in 1 mg/m3 PM2.5 group were significantly increased （all P 〈 0. 05 ）. Conclusion PM2.5 exposure can increase cerebral infarction volume in stroke prone spontaneously hypertensive rats, and promote further activation of autophagy after cerebral ischemia and aggravate ce

关 键 词：脑卒中 大气细颗粒物PM2.5 自噬 

分 类 号：R743.3[医药卫生—神经病学与精神病学]