中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (9): 2019-2026.doi: 10.4103/1673-5374.390951

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

C1q肿瘤坏死因子相关蛋白6减轻糖尿病小鼠的脑缺血再灌注损伤的作用机制

  

  • 出版日期:2024-09-15 发布日期:2024-01-26
  • 基金资助:
    国家自然科学基金项目（82102295，82071339，82001119和81901994）

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

Bo Zhao1, #, Mei Li1, #, Bingyu Li1, #, Yanan Li1, Qianni Shen1, Jiabao Hou1, Yang Wu1, Lijuan Gu2, *, Wenwei Gao3, *   

  1. 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; 2Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; 3Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
  • Online:2024-09-15 Published:2024-01-26
  • Contact: Wenwei Gao, MD, gaowenwei@whu.edu.cn; Lijuan Gu, MD, PhD, gulijuan@whu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82102295 (to WG), 82071339 (to LG), 82001119 (to JH), and 81901994 (to BZ).

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摘要：

有研究发现，C1q肿瘤坏死因子相关蛋白6可通过减轻氧化损伤来减轻小鼠的肾缺血再灌注损伤，但其在大脑中的作用尚未得到进一步研究。为研究C1q肿瘤坏死因子相关蛋白6对糖尿病脑缺血再灌注损伤的作用，实验首先阻塞糖尿病小鼠大脑中动脉建立糖尿病脑缺血再灌注损伤模型。侧脑室注射C1q肿瘤坏死因子相关蛋白6过表达腺相关病毒，可见模型小鼠脑组织中氧化损伤和炎症明显减轻，神经元凋亡显著减少。体外实验中，C1Q肿瘤坏死因子相关蛋白6敲除可减轻高糖缺氧模拟糖尿病脑缺血再灌注损伤的大脑皮质神经元中氧化损伤、炎症反应和细胞凋亡。为探索C1Q肿瘤坏死因子相关蛋白6的作用机制，对脑组织特异性Sirtuin 1敲除小鼠进行糖尿病脑缺血再灌注损伤，发现C1Q肿瘤坏死因子相关蛋白6的保护作用是依赖于Sirtuin 1信号通路激活实现的。综上所述，C1Q肿瘤坏死因子相关蛋白6可减轻糖尿病小鼠的脑缺血再灌注损伤，且其机制与活化Sirtuin 1信号通路有关。

https://orcid.org/0000-0003-4405-0168 (Wenwei Gao); https://orcid.org/0000-0003-1928-8772 (Lijuan Gu)

关键词: 大脑, 脑细胞凋亡, C1q肿瘤坏死因子相关蛋白6, 糖尿病, 炎症, 缺血再灌注损伤, 神经元, 神经保护, 氧化损伤, Sirt1

Abstract: Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Key words: brain, C1q/tumor necrosis factor-related protein-6, cerebral apoptosis, diabetes, inflammation, ischemia/reperfusion injury, neuron, neuroprotection, oxidative damage, Sirt1