肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制

doi:10.3969/j.issn.1006-7795.2023.01.009

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (1): 54-61.doi: 10.3969/j.issn.1006-7795.2023.01.009

• 脑血管病的基础与临床研究 • 上一篇下一篇

肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制

秦琳慧¹, 李宁¹, 杨宇², 杨勇², 任长虹^1*

1.首都医科大学宣武医院低氧适应转化医学北京市重点实验室,北京 100053;
2.北京中医药大学中医学院,北京 100096

收稿日期:2022-11-01 出版日期:2023-02-21 发布日期:2023-01-13
基金资助:
国家自然科学基金(81971114, 82274401)。

Limb remote ischemic perconditioning combined with remote ischemic postconditioning promotes neurogenesis in rat models of ischemic stroke

Qin Linhui¹, Li Ning¹, Yang Yu², Yang Yong², Ren Changhong^1*

1. Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
2. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100096, China

Received:2022-11-01 Online:2023-02-21 Published:2023-01-13
Contact: *E-mail:rench@xwhosp.org
Supported by:
National Natural Science Foundation of China (81971114, 82274401).

摘要/Abstract

摘要： 目的探讨肢体远隔缺血期适应(per-conditioning,PerC)联合后适应(post-conditioning,PostC)对缺血性脑卒中后神经再生的作用,并明确PerC联合PostC对脂肪酸β-氧化(fatty acid β-oxidation,FAO)限速酶——肉毒碱棕榈酰转移酶(carnitine palmitoyl transferase 1A,CPT1A)的影响。方法对成年雄性SD大鼠进行大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)造模,MCAO模型后30 min进行肢体远隔缺血期适应治疗(PerC),再灌注24 h后重复进行肢体远隔缺血适应(PostC),1次/d,直到取材。再灌注14 d后对大鼠进行神经功能评分,通过免疫组织化学染色检测室管膜下区(subependymal ventricular zone, SVZ)神经再生情况,通过酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测CPT1A的表达。结果与MCAO组及PerC/PostC组比较,PerC+PostC组大鼠,身体不对称运动行为评分降低,神经干细胞的数量以及向梗死区迁移的细胞数量增加。Pearson相关性分析显示,神经干细胞的数量与神经功能呈负相关(r=-0.917 9, P<0.0001)。然而,迁移到基底节区的神经干细胞的凋亡数量在各组之间差异无统计学意义。机制研究显示,PerC+PostC组CPT1A的蛋白水平显著增加。结论 PerC联合PostC治疗能够通过增加神经干细胞的数量改善神经功能,神经干细胞的脂肪酸氧化可能是其促进神经干细胞迁移的机制之一。

关键词: 缺血性脑卒中, 肢体远隔缺血适应, 神经再生, 脂肪酸β-氧化

Abstract: Objective To explore comfirm the effect of limb remote ischemic per-conditioning (PerC) combined with post-conditioning (PostC) on neurogenesis after ischemic stroke, and to explore the effect of PerC combined with PostC on the rate-limiting enzyme of fatty acid β-oxidation (FAO): carnitine palmitoyl transferase 1A (CPT1A). Methods Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Limb remote ischemic conditioning was applied 30 min after the MCAO model, followed by repeated short episodes of remote ischemic conditioning 24 h after reperfusion (post-conditioning). The neurogenesis in the subependymal ventricular zone(SVZ) region was analyzed with immunohistochemistry staining, and the expression of CPT1A was analyzed with enzyme linked immunosorbent assay(ELISA). Results PerC+PostC treatment significantly improved neurological function and increased the number of neural stem cells (NSCs) and the number of cells that migrated to the infarct area compared to the MCAO and PerC/PostC groups. Pearson correlation analysis showed that the number of neural stem cells had a negative correlation with neurological function. However, the number of apoptotic NSCs that migrated to the basal ganglia did not differ significantly between groups. Further mechanism studies showed that the treatment with PerC+PostC significantly increased the protein level of CPT1A. Conclusion PerC combined with PostC treatment can improve neurological function by increasing the number of NSCs. FAO of NSCs may be one of its mechanisms to promote the migration of NSCs.

Key words: ischemic stroke, limb remote ischemic conditioning, neurogenesis, fatty acid β-oxidation

中图分类号:

R743.3

秦琳慧, 李宁, 杨宇, 杨勇, 任长虹. 肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制[J]. 首都医科大学学报, 2023, 44(1): 54-61.

Qin Linhui, Li Ning, Yang Yu, Yang Yong, Ren Changhong. Limb remote ischemic perconditioning combined with remote ischemic postconditioning promotes neurogenesis in rat models of ischemic stroke[J]. Journal of Capital Medical University, 2023, 44(1): 54-61.

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肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制

Limb remote ischemic perconditioning combined with remote ischemic postconditioning promotes neurogenesis in rat models of ischemic stroke

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