亚低温处理对大鼠脑缺血模型皮层神经元损伤和miR-199a表达水平的影响  

Effect of mild hypothermia on neuronal damage and the expression of miR-199a in the cerebral ischemic penumbral

作　　者：王金领[1] 李洪忠 侯立朝 刘姗姗 蔡铁良 胡宏强 袁欣 都继微 邓斌 Wang Jinling;Li Hongzhong;Hou Lichao;Liu Shanshan;Cai Tieliang;Hu Hongqiang;Yuan Xin;Du Jiwei;Deng Bin(Department of Emergencey, Zhongshan Hospital;Department of Anesthesiology, Xiangan Hospital;Nursing Department, Xiangan Hospital;Department of Anesthesiology, Chenggong Hospital, Xiamen Univeristy, Xiamen 361000;Xiamen Garrison Command, Xiamen 361003, China)

机构地区：[1]厦门大学附属中山医院急诊科,厦门361000 [2]厦门警备区保障处,厦门361003 [3]厦门大学附属翔安医院麻醉科,厦门361000 [4]厦门大学附属成功医院麻醉科,厦门361000 [5]厦门大学附属翔安医院护理部,厦门361000

出　　处：《神经解剖学杂志》2018年第2期191-197,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81501207);陕西省科学技术研究发展计划项目(陕2016YFJH2-04);厦门市科技计划项目(3502Z20174034)

摘　　要：目的:探讨局部亚低温(mildhypothermia,MHT)处理对大脑皮层缺血半暗带内mi R-199a表达的影响及其神经保护作用。方法:取成年雄性Sprague-Dawley大鼠,制作大脑中动脉栓塞(middle cerebral arterial occlusion,MCAO)模型,在再灌注后30 min时大鼠头部进行亚低温处理3 h。再灌注后6 h,24 h和72 h时利用q RTPCR检测大脑皮层半暗带内mi R-199a表达;再灌注后24 h时进行神经功能缺陷评分并测量脑水肿情况;再灌注后24 h时制备脑组织冰冻切片,分别进行NISSL和FJC染色,观察神经元损伤及变性情况。结果:(1)再灌注后24 h时MCAO组mi R-199a表达明显多于再灌注后6 h和72 h时MCAO组mi R-199a表达(P<0.05)。再灌注后6 h、24 h和72 h时,与各Sham组亚组相比,各MCAO组亚组mi R-199a表达明显增加(P<0.05);与各MCAO组亚组相比,各MCAO+MHT组亚组mi R-199a表达明显减少(P<0.05)。(2)再灌注24 h时,与MCAO+MHT组相比,MCAO组及MCAO+MHT+mi R-199a mimics组模型动物神经功能缺陷评分显著增加(P<0.05),脑组织含水量明显增多(P<0.05),半暗带内正常神经元数量显著减少(P<0.05),变性神经元数量显著增加(P<0.05)。结论:局部亚低温处理可通过抑制大脑皮层缺血半暗带内mi R-199a表达,减轻脑水肿,缓解神经元变性和损伤,从而发挥神经保护作用。Objective： To study the effect of mild hypothermia treatment on miR-199 a expression in the ischemic penumbra after MCAO and on the neuroprotection. Methods： Adult male Sprague-Dawley rats were used. The middle cerebral arterial occlusion（ MCAO） model was established. At 30 min after reperfusion,the head of rats treated with mild hypothermia for 3 h. At 6 h,24 h and 72 h after reperfusion,the expression of miR-199 a was tested in the penumbra. At 24 h after reperfusion,the brain water content and neurological deficit scores（ NDS） were evaluated. At 24 h after reperfusion,the NISSL and FJC staining in the penumbra was measured. Results：（ 1） Compared with the MCAO group at 24 h after reperfusion,the expression of miR-199 a was decreased in MCAO group at 6 h and 72 h after reperfu-sion（ P〈0. 05）. At 6 h,24 h and 72 h after reperfusion,compared with every Sham group,the expression of miR-199 a was increased in every MCAO group（ P〈0. 05）; Compared with every MCAO group,the expression of miR-199 a was decreased in every MCAO ＋ MHT group（ P〈0. 05）.（ 2） At 24 h after reperfusion,compared with MCAO ＋ MHT group,the NDS was higher（ P〈0. 05）,the water content was more（ P〈0. 05）,the density of normal neurons in the ischemic penumbra was decreased（ P〈0. 05） and the number of FJC-positive neurons was less（ P〈0. 05） in MCAO group and in MCAO ＋ MHT ＋ miR-199 a mimics group. Conclusion： Mild hypothermia treatment attenuated brain damage and enhanced neural function recovery by alleviating neuronal damage and degeneration through inhibiting miR-199 a expression in the ischemic penumbra after cerebral ischemia injury.

关 键 词：脑缺血再灌注损伤 亚低温 miR-199a 神经保护作用 神经元 

分 类 号：R-332[医药卫生] R743