中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (9): 1716-1723.doi: 10.4103/1673-5374.276343

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Akt/糖原合酶激酶3β途径参与白细胞介素4保护脑缺血再灌注损伤

  

  • 出版日期:2020-09-08 发布日期:2020-09-23

The Akt/glycogen synthase kinase-3β pathway participates in the neuroprotective effect of interleukin-4 against cerebral ischemia/reperfusion injury

Mei Li1 , Wen-Wei Gao2, * , Lian Liu1 , Yue Gao3 , Ya-Feng Wang1 , Bo Zhao1 , Xiao-Xing Xiong4, *   

  1. 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China 2 Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China 3 Department of Personnel, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China 4 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
  • Online:2020-09-08 Published:2020-09-23
  • Contact: Wen-Wei Gao, MD, wenwei_gao@163.com; Xiao-Xing Xiong, PhD, MD, xiaoxingxiong@whu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81901994 (to BZ) and 81571147 (to XXX); the Natural Science Foundation of Hubei Province, China, No. 2019CFC847 (to WWG); the Fundamental Research Funds for the Central Universities, China, No. 2042018kf0149 (to ML).

摘要:

orcid:  0000-0003-4405-0168 (Wen-Wei Gao) 

         0000-0001-6983-8547 (Xiao-Xing Xiong)

Abstract: Interleukin-4 (IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short- and long-term prognosis of neurological function. The Akt (also called protein kinase B, PKB)/glycogen synthase kinase-3β (Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex (10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/ GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China (approval No. WDRY2017-K037) on March 9, 2017.

Key words: Akt/glycogen synthase kinase-3β pathway, apoptosis, autophagy, cerebral ischemia/reperfusion injury, infarct volume, interleukin-4, neuroprotection, oxidative stress