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早期有氧运动通过上调热休克蛋白A5的表达促进脑缺血/再灌注大鼠神经功能恢复。

Early Aerobic Exercise Promotes Neurological Function Recovery of Rats after Cerebral Ischemia/Reperfusion by Upregulating the Expression of Heat Shock Protein A5.

作者信息

Peng Zhi-Feng, Zhang Nai-Bao, Meng Jian, Zhang Ji-Hong

机构信息

Department of Physiology, School of Medicine, Shanxi Datong University, Datong, 037009, China.

Department of Neurology, Luliang People's Hospital, Luliang, 033000, China.

出版信息

Curr Med Sci. 2022 Apr;42(2):267-273. doi: 10.1007/s11596-022-2537-0. Epub 2022 Mar 19.

DOI:10.1007/s11596-022-2537-0
PMID:35305213
Abstract

OBJECTIVE

The neuroprotective function of heat shock protein A5 (HSPA5) in ischemic stroke has been confirmed. This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from cerebral ischemia/reperfusion and to determine whether these effects are associated with the expression level of HSPA5 in the ischemic penumbra.

METHODS

A total of 72 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion (MCAO)-Ex, n=18], ischemia and sedentary group (MCAO-St, n=18), sham-surgery and exercise group (Sham-Ex, n=18), or sham-surgery and sedentary group (Sham-St, n=18). The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 min, whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO. Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 min once a day for 5 consecutive days. After reperfusion, the motor function of the rats was scored by the Bederson neurological function test, balance beam test, and screen test. Nissl staining was conducted to assess morphological and structural change of nerve cells in the ischemic penumbra. The reverse transcription-quantitative polymerase chain reaction was applied to detect the mRNA expression of HSPA5. Western blot analysis was conducted to determine the protein expression of HSPA5. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was carried out in the ischemic penumbra after MCAO.

RESULTS

Rats receiving early treadmill exercise had lower Bederson neurological function, balance beam, and screen test scores on the 3rd, 7th, and 14th days after MCAO; in addition, more neurons survived in the ischemic penumbra after MCAO, and higher mRNA and protein expression of HSPA5 and fewer TUNEL-positive stained cells were observed.

CONCLUSION

Our study demonstrated that early aerobic exercise can improve neurological function recovery after ischemia/reperfusion. Furthermore, the increased level of HSPA5 in the ischemic penumbra might be one of the mechanisms of enhanced neurological function recovery.

摘要

目的

热休克蛋白A5(HSPA5)在缺血性卒中中的神经保护功能已得到证实。本研究旨在探讨早期有氧运动对脑缺血/再灌注后神经功能恢复的影响,并确定这些影响是否与缺血半暗带中HSPA5的表达水平相关。

方法

将72只雄性Sprague-Dawley大鼠随机分为缺血运动组[大脑中动脉闭塞(MCAO)-Ex,n = 18]、缺血静息组(MCAO-St,n = 18)、假手术运动组(Sham-Ex,n = 18)或假手术静息组(Sham-St,n = 18)。MCAO-Ex组和MCAO-St组进行60分钟的MCAO,而Sham-Ex组和Sham-St组进行相同的手术但不进行MCAO。MCAO-Ex组和Sham-Ex组的大鼠随后每天在跑步机上跑30分钟,连续跑5天。再灌注后,通过Bederson神经功能测试、平衡木测试和筛板测试对大鼠的运动功能进行评分。进行尼氏染色以评估缺血半暗带中神经细胞的形态和结构变化。应用逆转录-定量聚合酶链反应检测HSPA5的mRNA表达。进行蛋白质印迹分析以确定HSPA5的蛋白表达。在MCAO后对缺血半暗带进行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色。

结果

接受早期跑步机运动的大鼠在MCAO后第3天、第7天和第14天的Bederson神经功能、平衡木和筛板测试评分较低;此外,MCAO后缺血半暗带中有更多神经元存活,观察到HSPA5的mRNA和蛋白表达较高,且TUNEL阳性染色细胞较少。

结论

我们的研究表明,早期有氧运动可改善缺血/再灌注后的神经功能恢复。此外,缺血半暗带中HSPA5水平的升高可能是神经功能恢复增强的机制之一。

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