Effect of autophagy on recovery of neurological dysfunction in rats after cerebral ischemia-reperfusion injury
10.3760/cma.j.issn.1671-8925.2018.02.004
- VernacularTitle:自噬对脑缺血再灌注损伤后神经功能障碍恢复的影响
- Author:
He HE
1
;
Guozhi HUANG
;
Qing ZENG
;
Yiqiu LIN
;
Hongxin LIN
Author Information
1. 南方医科大学珠江医院康复医学科
- Keywords:
Cerebral ischemia reperfusion injury;
Autophagy;
Neurological dysfunction
- From:
Chinese Journal of Neuromedicine
2018;17(2):124-129
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the development and progression of autophagy,and investigate the effect of autophagy on recovery of neurological dysfunction in rats after cerebral ischemia-reperfusion injury.Methods Preparation of middle cerebral artery occlusion (MCAO) models was performed by Longa method.(1) Forty-two SD rats were randomly assigned to blank control 1 group (n=9) and MCAO 1 group (n=33),and the rats of the MCAO 1 group were randomly divided into 6,12,48 and 72 h subgroups (n=6) and 24 h subgroup (n=9) according to the reperfusion times;the ultrastructural changes and autophagosome formation in hippocarnpal tissues of the blank control 1 group (n=3) and 24-h-reperfusion MCAO 1 subgroup (n=3) were observed under transmission electron microscope;the expressions of microtubule associated proteins light chain-3 (LC3)-Ⅱ,LC3-Ⅰ and Beclin-1 in the hippocampal tissues of each group (n=6) were detected by Western blotting.(2) Eighteen SD rats were randomly divided into blank control 2 group,MCAO 2 group and 3-methyladenine (3-MA,autophagy inhibitor) group (60 min prior to MCAO,injection of 10 μL [600 nmoL] 3-MA dilution into the lateral ventricle by stereotactic technique,n=6);the neurological rehabilitation of rats was analyzed by modified neurological severity scale (mNSS) one,3,5 and 7 d after reperfusion;the morphological changes and number of apoptotic cells in the hippocampal tissues were observed by HE staining 7 d after reperfusion.Results (1) The formation ofautophagy in the 24-h-reperfusion MCAO 1 subgroup was clearly observed under microscope;as compared with blank control 1 group,the ratio of LC3-Ⅱ/Ⅰ (excepted for 72-h-reperfusion MCAO 1 subgroup) and Beclin-1 expression in the hippocampus of 6,12,24 and 48-h-reperfusion MCAO 1 subgroups were significantly increased (P＜0.05);as compared with those in the 24-h-reperfusion MCAO 1 subgroup,the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 expression in the hippocampus of 6,12,48 and 72-h-reperfusion MCAO 1 subgroups were significantly decreased (P＜ 0.05).(2) As compared with those the MCAO 2 group,the mNSS scores of 3-MA group were significantly decreased 3,5 and 7 d after surgery (P＜0.05);HE staining indicated that the injury of neurons in the hippocampus of 3-MA group was alleviated,and the number of apoptotic cells in the 3-MA group was significantly smaller than that in the MCAO 2 group ([14.00±2.10]/field vs.[37.83± 2.64]/field,P＜0.05).Conclusion Cerebral ischemia-reperfusion injury can activate autophagy,by which it can alleviate brain damage and improve its neurological dysfunction in rats after cerebral ischemia-reperfusion injury.
