迷走神经刺激通过自噬机制对短暂性大脑中动脉栓塞大鼠模型神经保护作用的实验研究  

Experimental study of the neuroprotective effect of vagus nerve stimulation on middle cerebral artery occlusion rat model through the mechanism of autophagy

作　　者：洪春永[1] 蔡秋菊 曾有福 吴欣宇[1] 李清金 林进皇 HONG Chun-yong;CAI Qiu-ju;ZENG You-fu(Department of Neurology,The 175th Hospital of PLA（Southeast Hospital Affiliated to Xiamen University）,Zhangzhou Fujian 363000,China)

机构地区：[1]中国人民解放军第一七五医院暨厦门大学附属东南医院神经内科,福建漳州363000

出　　处：《临床和实验医学杂志》2018年第22期2370-2374,共5页Journal of Clinical and Experimental Medicine

基　　金：中国人民解放军第一七五医院青年苗圃基金项目资助(编号:16Y001)

摘　　要：目的探讨迷走神经刺激对大鼠短暂性大脑中动脉栓塞(t-MCAO)模型的神经保护作用及其可能的机制。方法将雄性SD大鼠60只,随机平分为3组,即迷走神经刺激组(VNS组,造模后予迷走神经刺激)、模型组(重复VNS组步骤但不刺激迷走神经)及假手术组(重复VNS组步骤,但不栓塞大脑中动脉及刺激迷走神经)。其中,采用线栓法将大脑中动脉闭塞,术后2 h拔出栓线,建立t-MCAO模型。各组给予相应操作流程后24 h,记录神经行为学评分、计算脑梗死体积及观察脑皮质区LC3-Ⅱ、Beclin1的表达。结果模型组神经行为学评分、脑梗死体积较假手术组均显著恶化(P <0. 05),VNS组神经行为学评分、脑梗死体积较模型组有改善(P <0. 05),但仍差于假手术组(P<0. 05)。相对于假手术组,模型组LC3-Ⅱ、Beclin1表达显著升高(P <0. 05),VNS组LC3-Ⅱ、Beclin1表达水平相对于模型组显著降低(P <0. 05),但仍高于假手术组(P <0. 05)。结论迷走神经刺激可能通过调控自噬激活水平发挥对大鼠短暂性脑缺血损伤的神经保护作用。Objective To investigate the neuroprotective effects and mechanism of vagal nerve stimulation （VNS） in a rat transient middle cerebral artery occlusion model. Methods 60 male SD rats were randomly divided into three groups ： VNS group （ n = 20） , model group （n=20） , SHAM operation group （ n= 20）. The model of rat transient focal cerebral ischemia was induced by the intraluminal suture method. The model group repeated the steps of the VNS - treated group, but did not stinmlate. The sham operation group repeated the experimental steps, but it neither embolized the vessels nor stinmlated nerves. The rats were sacrificed after 24 h. Indices of neurobehavioral scores, infarction rate were measured. The expressions of LC3 -Ⅱ and Beelinl in brain tissue were determined by inmmnohistoehemistry staining. Results Compared with the sham operation group, Indices of neurobehavioral scores, infarction rate were significantly improved （ P 〈 0.05）. Tbere were also significant differences between VNS group and model group （ P 〈 0.05）. Compared with model group and sham operation group, the number of positive cells of LC3 - Ⅱ and Beelinl in the VNS - treated group decreased significantly （ P 〈 0.05）. Compared with the sham operation group, it were significantly improved in Model group （ P 〈 0.05 ）. Conclusion The neuroproteetive mechanism of VNS for cerebral isehemia may be associated with the inhibition of autophagy.

关 键 词：大鼠 短暂性大脑中动脉栓塞模型 迷走神经刺激 神经保护 自噬 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]