痘苗病毒致炎兔皮提取物对脑缺血再灌注脑损伤大鼠凋亡和神经炎症的影响

doi:10.3969/j.issn.1006-9771.2020.09.008

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (9): 1038-1044.doi: 10.3969/j.issn.1006-9771.2020.09.008

痘苗病毒致炎兔皮提取物对脑缺血再灌注脑损伤大鼠凋亡和神经炎症的影响

陈小平,王明洋,马登磊,龚诗立,张丽,李雅莉,李林,胡朝英,张兰()

首都医科大学宣武医院药学部,国家老年疾病临床医学研究中心,神经变性病教育部重点实验室,北京市神经药物工程研究中心,北京市 100053

收稿日期:2019-12-24 修回日期:2020-01-17 出版日期:2020-09-25 发布日期:2020-09-24
通讯作者: 张兰 E-mail:lanizhg@126.com
作者简介:陈小平(1995-),男,汉族,江西新余市人,硕士研究生,主要研究方向：神经药理学。|张兰(1972-),女,教授,博士生导师,主要研究方向：神经药理学、中药药理学。
基金资助:
1.国家自然科学基金项目(81903880);2.北京市卫生系统高层次卫生技术人才项目(2014-2-014);3.北京市首都科技领军人才培养工程项目(Z191100006119017);4.北京市医院管理中心“登峰”计划专项(DFL20190803);5.北京市博士后工作经费资助项目(2018-ZZ-105);6.中国博士后基金项目(2019M650776)

Effects of Analgecine on Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury Rats

CHEN Xiao-ping,WANG Ming-yang,MA Deng-lei,GONG Shi-li,ZHANG Li,LI Ya-li,LI Lin,HU Chao-ying,ZHANG Lan()

Department of Pharmacy, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China

Received:2019-12-24 Revised:2020-01-17 Published:2020-09-25 Online:2020-09-24
Contact: ZHANG Lan E-mail:lanizhg@126.com
Supported by:
National Natural Science Foundation of China(81903880);Beijing High-level Health and Technical Personal Plan(2014-2-014);Capital Science and Technology Leading Talent Training Project(Z191100006119017);Beijing Hospitals Authority Ascent Plan(DFL20190803);Beijing Postdoctoral Research Foundation(2018-ZZ-105);China Postdoctoral Science Foundation(2019M650776)

摘要/Abstract

摘要：

目的探究痘苗病毒致炎兔皮提取物(AGC)对大鼠脑缺血再灌注损伤的保护作用及机制。
方法 Sprague-Dawley大鼠61只分为假手术组(n = 11)、假手术给药组(n = 11)、模型组(n = 20)和模型给药组(n = 19)。模型组和模型给药组线栓法脑缺血1.5 h后恢复灌注。模型组和模型给药组各有2只造模不成功。再灌注3 h后,假手术给药组和模型给药组尾静脉每天注射AGC 20 U/kg,假手术组和模型组尾静脉注射等体积生理盐水。给药48 h后每组取4只大鼠Western blotting方法检测脑组织热休克蛋白(HSP70)、Bcl-2和Bax表达;给药7 d后,行抓握牵引实验;各组取4只大鼠,免疫组化法观察离子钙结合蛋白(Iba1)阳性和胶质纤维酸性蛋白(GFAP)阳性表达。
结果与模型组相比,模型给药组抓握时间明显延长(P < 0.01),HSP70和Bcl-2表达明显升高( P < 0.01),Iba1阳性和GFAP阳性面积下降( P < 0.05)。
结论 AGC能促进脑缺血再灌注损伤大鼠运动功能恢复,可能与抑制细胞凋亡和神经炎症反应有关。

关键词: 缺血性脑卒中, 脑缺血再灌注, 痘苗病毒致炎兔皮提取物, 运动, 凋亡, 炎症, 大鼠

Abstract:

Objective To observe the effects of Analgecine (AGC) on middle cerebral artery ischemia-reperfusion injury in rats and its mechanism.
Methods A total of 61 Sprague-Dawley rats were divided into sham group (n = 11), sham-AGC group (n = 11), model group (n = 20) and model-AGC group (n = 19). The model group and the model-AGC group were occluded the middle cerebral arteries for 1.5 hours and reperfused (2 rats in each group unsuccessful). The sham-AGC group and the model-AGC group were injected AGC 20 U/kg through tail-vein, while the sham group and the model group were injected saline of same volume. Four rats in each group were tested heat shock proteins 70 (HSP70), Bcl-2 and Bax in brain with Western blotting 48 hours after injection. The other rats were assessed with Prehensile Traction Test seven days after injection, and then, four of each group were detected ionized calcium binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expression with immunohistochemistry.
Results The prehensile time increased in the model-AGC group compared with that of the model group (P < 0.01), with the increase of HSP70 and Bcl-2 ( P < 0.01) and decrease of Iba1 and GFAP expression ( P < 0.05).
Conclusion AGC may promote the recovery of motor function in rats with cerebral ischemia-reperfusion injury, which may associate with inhibiting cell apoptosis and neruoinflammatory response.

Key words: ischemic stroke, cerebral ischemia-reperfusion, Analgecine, motor, apoptosis, inflammation, rats

陈小平,王明洋,马登磊,龚诗立,张丽,李雅莉,李林,胡朝英,张兰. 痘苗病毒致炎兔皮提取物对脑缺血再灌注脑损伤大鼠凋亡和神经炎症的影响[J]. 《中国康复理论与实践》, 2020, 26(9): 1038-1044.

CHEN Xiao-ping,WANG Ming-yang,MA Deng-lei,GONG Shi-li,ZHANG Li,LI Ya-li,LI Lin,HU Chao-ying,ZHANG Lan. Effects of Analgecine on Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury Rats[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(9): 1038-1044.

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组别	n	评分
假手术组	7	4.71±0.488
假手术给药组	7	4.86±0.378
模型组	8	1.63±0.517^a
模型给药组	9	2.89±1.054^b
F值		37.590
P值		< 0.001

组别	n	HSP70(/β-actin)	Bcl-2(/β-actin)	Bax(/β-actin)	Bcl-2/Bax
假手术组	4	1.06±0.068	1.10±0.086	0.94±0.202	1.21±0.176
假手术给药组	4	1.07±0.117	1.10±0.043	0.96±0.017	1.14±0.044
模型组	4	0.63±0.114^a	0.69±0.090^b	1.10±0.082	0.63±0.104^c
模型给药组	4	1.23±0.310^d	1.11±0.214^d	1.01±0.099	1.10±0.141^e
F值		8.323	10.790	1.385	17.100
P值		0.003	0.001	0.295	< 0.001

组别	n	GFAP	Iba1
假手术组	4	10.48±5.199	6.00±2.499
假手术给药组	4	6.76±5.073	4.78±1.790
模型组	4	26.27±1.996^a	20.06±3.447^a
模型给药组	4	16.53±3.218^b	12.40±4.750^b
F值		17.300	17.940
P值		< 0.001	< 0.001

痘苗病毒致炎兔皮提取物对脑缺血再灌注脑损伤大鼠凋亡和神经炎症的影响

Effects of Analgecine on Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury Rats

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