迷走神经刺激对脑缺血再灌注大鼠磷酸腺苷活化蛋白激酶-沉默信息调节因子2相关酶1自噬通路的影响

doi:10.3969/j.issn.1006-9771.2020.07.007

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (7): 775-779.doi: 10.3969/j.issn.1006-9771.2020.07.007

迷走神经刺激对脑缺血再灌注大鼠磷酸腺苷活化蛋白激酶-沉默信息调节因子2相关酶1自噬通路的影响

魏海萍,郭佳,王欢,葛朝明()

兰州大学第二医院神经内科,甘肃兰州市 730030

收稿日期:2019-10-29 修回日期:2020-01-16 出版日期:2020-07-25 发布日期:2020-07-24
通讯作者: 葛朝明 E-mail:sjnk11@sina.com
作者简介:魏海萍(1983-),女,汉族,甘肃白银市人,博士研究生,主治医师,主要研究方向：缺血性脑卒中干预措施及分子机制。|葛朝明(1963-),男,汉族,甘肃兰州市人,教授,博士研究生导师,主要研究方向：高压氧神经保护作用及机制。
基金资助:
甘肃省自然科学基金项目(17JR5RA240)

Effects of Vagus Nerve Stimulation on Adenosine Monophosphate Activated Protein Kinase-Silent Mating Type Information Regulation 2 Homolog 1 Pathway in Ischemia-reperfusion Rats

WEI Hai-ping,GUO Jia,WANG Huan,GE Zhao-ming()

Department of Neurology, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China

Received:2019-10-29 Revised:2020-01-16 Published:2020-07-25 Online:2020-07-24
Contact: GE Zhao-ming E-mail:sjnk11@sina.com
Supported by:
Natural Science Funds of Gansu(17JR5RA240)

摘要/Abstract

摘要：

目的探讨迷走神经刺激(VNS)在缺血性脑卒中缺血半影区细胞自噬中的作用。方法 Sprague-Dawley大鼠56只分为正常组(n = 14)、假手术组(n = 14)、模型组(n = 14)和VNS组(n = 14)。模型组和VNS组线栓法建立缺血1 h再灌注模型,VNS组于缺血0.5 h时行左侧VNS。再灌注24 h后,TTC染色法观察脑梗死体积,Longa评分观察大鼠神经损伤程度,Western blotting检测Beclin-1水平和微管相关蛋白1轻链3 (LC3)-Ⅱ/Ⅰ比值,并检测磷酸腺苷活化蛋白激酶(AMPK)磷酸化水平和沉默信息调节因子2相关酶1 (Sirt1)蛋白水平。结果与假手术组相比,模型组缺血半影区Beclin-1、LC3-Ⅱ/Ⅰ、AMPK磷酸化水平和Sirt1蛋白表达均显著下降(P < 0.001)。与模型组相比,VNS组脑梗死体积显著减小( P < 0.001),Longa评分降低( P < 0.05),缺血半影区Beclin-1水平和LC3-Ⅱ/Ⅰ比值显著上升( P < 0.001),AMPK磷酸化水平和Sirt1蛋白水平显著上升( P < 0.001)。结论 VNS通过调节AMPK-Sirt1自噬通路,减轻大鼠缺血性脑损伤。

关键词: 缺血性脑卒中, 迷走神经刺激, 自噬, 磷酸腺苷活化蛋白激酶, 信息通路

Abstract:

Objective To investigate the effect of vagus nerve stimulation (VNS) on the autophagy in penumbra of rats after middle cerebral artery occlusion (MCAO). Methods A total of 56 Sprague-Dawley rats were divided into control group (n = 14), sham group (n = 14), model group (n = 14) and VNS group (n = 14). The model group and VNS group accepted MCAO for one hour, then reperfusion, and VNS group accepted VNS in the left as MCAO for 0.5 hour. Their infarct volume was detected with TTC staining, neurological impairment was assessed with Longa's score, and the expression of Beclin-1, microtubule-associated protein 1 light chain 3 (LC3)-II/I, phosphorylated adenosine monophosphate activated protein kinase (P-AMPK) and silent mating type information regulation 2 homolog 1 (Sirt1) were detected with Western blotting 24 hours after reperfusion.Results Compared with the sham group, the infarct volume and Longa's score increased in the model group, while the expression of Beclin-1, LC3-II/I, P-AMPK and Sirt1 decreased significantly (P < 0.001). Compared with the model group, the infarct volume and Longa's score reduced ( P < 0.05) in VNS group, while the expression of Beclin-1, LC3-II/I, P-AMPK and Sirt1 increased significantly ( P < 0.001). Conclusion VNS may alleviate cerebral ischemic injury in rats through AMPK-Sirt1 pathway.

Key words: ischemic stroke, vagus nerve electrostimulation, autophagy, adenosine monophosphate activated protein kinase, pathway

中图分类号:

R743.3

魏海萍,郭佳,王欢,葛朝明. 迷走神经刺激对脑缺血再灌注大鼠磷酸腺苷活化蛋白激酶-沉默信息调节因子2相关酶1自噬通路的影响[J]. 《中国康复理论与实践》, 2020, 26(7): 775-779.

WEI Hai-ping,GUO Jia,WANG Huan,GE Zhao-ming. Effects of Vagus Nerve Stimulation on Adenosine Monophosphate Activated Protein Kinase-Silent Mating Type Information Regulation 2 Homolog 1 Pathway in Ischemia-reperfusion Rats[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(7): 775-779.

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组别	n	Longa评分
正常组	5	0.600±0.490
假手术组	5	0.800±0.400
模型组	5	7.200±2.040^a
VNS组	5	4.600±0.800^a,b
F值		25.065
P值		< 0.001

组别	n	Beclin-1	LC3-II/LC3-I	P-AMPK	Sirt1
正常组	5	100.00±0.00	100.00±0.00	100.00±0.00	100.00±0.00
假手术组	5	100.68±4.46	101.66±9.90	96.40±3.91	99.23±9.27
模型组	5	34.56±5.95^a	27.69±5.24^a	25.64±3.71^a	29.22±4.15^a
VNS组	5	76.10±7.47^a,b	66.29±8.53^a,b	65.80±2.65^a,b	66.57±8.67^a,b
F值		138.623	82.833	481.782	82.544
P值		< 0.001	< 0.001	< 0.001	< 0.001

迷走神经刺激对脑缺血再灌注大鼠磷酸腺苷活化蛋白激酶-沉默信息调节因子2相关酶1自噬通路的影响

Effects of Vagus Nerve Stimulation on Adenosine Monophosphate Activated Protein Kinase-Silent Mating Type Information Regulation 2 Homolog 1 Pathway in Ischemia-reperfusion Rats

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