中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (10): 1632-1639.doi: 10.4103/1673-5374.217337

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

糖原合酶激酶3β是糖尿病心肌缺血再灌注诱导脑损伤的重要因素？

  

  • 收稿日期:2017-09-22 出版日期:2017-10-15 发布日期:2017-10-15
  • 基金资助:

    国家自然科学基金（81471844）湖北省自然科学基金（2016CFB167）；中央高校基础科学研究基金（2042017kf0147）

 The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus

Bo Zhao1, Wen-wei Gao2, Ya-jing Liu1, Meng Jiang1, Lian Liu1, Quan Yuan1, Jia-bao Hou 1, Zhong-yuan Xia1   

  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
  • Received:2017-09-22 Online:2017-10-15 Published:2017-10-15
  • Contact: Zhong-yuan Xia, M.D.,xiazhongyuan2005@aliyun.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81471844; the Natural Science Foundation of Hubei Province of China, No. 2016CFB167; the Basic Scientific Research Foundation of Central Universities, No. 2042017kf0147.

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摘要：

心肌缺血再灌注可能会导致更为严重的脑损伤。糖原合酶激酶3β信号通路同时参与了心肌缺血再灌注和糖尿病的调控并起到重要作用，但其是否与糖尿病后心肌缺血再灌注诱导的脑损伤有关目前尚不清楚。为此，实验设计观察糖原合酶激酶3β对糖尿病大鼠心肌缺血再灌注致脑损伤的影响。首先采用链硫脲菌素诱导法建立糖尿病大鼠模型，采用冠状动脉左前降支结扎法建立心肌缺血再灌注大鼠模型，最后进行缺血后处理为在心肌缺血后再灌注前，先实施3个循环的再灌注/缺血。实验同时设正常非糖尿病大鼠进行对比。以免疫组织化学染色和Western Blot检测可见，心肌缺血再灌注后48 h，大鼠大脑皮质组织受损严重，Bax，白细胞介素6，8，TUNEL免疫阳性细胞和cleaved caspase-3蛋白表达增多，Bcl-2，白细胞介素10免疫阳性细胞和p-糖原合酶激酶3β蛋白表达降低。与正常非糖尿病大鼠相比较，糖尿病大鼠大脑皮质炎症因子白细胞介素6，8和凋亡因子Bax的免疫反应增加，但缺血后处理在一定程度上减轻了上述变化，如果术前10 min腹腔注射糖原合酶激酶3β抑制剂LiCl，可阻止后处理的保护作用。结果证实，心肌缺血后处理可减轻糖尿病后心肌缺血再灌注诱导的脑损伤，具体机制可能与糖原合酶激酶3β激活有关，顾可认为糖原合酶激酶3β是糖尿病心肌缺血再灌注诱导脑损伤的重要因素。

orcid:0000-0002-5807-9554(Zhong-yuan Xia)

关键词: 心肌缺血再灌注, 脑损伤, 糖原合酶激酶3&beta, , 缺血后处理, 糖尿病

Abstract:

Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus. However, the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear. In this study, we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats. Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin. Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery. Post-conditioning comprised three cycles of ischemia/reperfusion. Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion, the structure of the brain was seriously damaged in the experimental rats compared with normal controls. Expression of Bax, interleukin-6, interleukin-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, and cleaved caspase-3 in the brain was significantly increased, while expression of Bcl-2, interleukin-10, and phospho-glycogen synthase kinase 3 beta was decreased. Diabetes mellitus can aggravate inflammatory reactions and apoptosis. Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes. Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta. According to these results, glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

Key words: nerve regeneration, myocardial ischemia/reperfusion injury, brain injury, glycogen synthase kinase 3 beta, ischemic post-conditioning, diabetes mellitus, neural regeneration