中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 137-143.doi: 10.4103/1673-5374.314318

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Ki20227加剧局灶性脑缺血损伤后细胞凋亡、炎症反应和氧化应激

  

  • 出版日期:2022-01-05 发布日期:2021-09-18

Ki20227 aggravates apoptosis, inflammatory response, and oxidative stress after focal cerebral ischemia injury

Cheng Jiang1, 2, #, Ze-Ning Wang1, 2, #, Yu-Chen Kang1, 3, #, Yi Chen1, 2, Wei-Xin Lu1, Hai-Jun Ren1, Bo-Ru Hou1, *#br#   

  1. 1Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China; 2Institute of Neurology, Lanzhou University, Lanzhou, Gansu Province, China; 3Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu Province, China
  • Online:2022-01-05 Published:2021-09-18
  • Contact: Bo-Ru Hou, PhD, friend7412@126.com.
  • Supported by:
    his study was supported by the Natural Science Foundation of Gansu Province, China, Nos. 20JR5RA337 (to BRH), 20JR5RA336 (to HJR); Cuiying Graduate Supervisor Applicant Training Program of Lanzhou University Second Hospital, China, No. CYDSPY201902 (to BRH); Cuiying Students Research Ability Training Program of Lanzhou University Second Hospital, China, No. CYXZ2020-14 (to BRH); and Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital, China, No. CY2018-MS08 (to BRH).

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摘要：

小胶质细胞的存活依赖于集落刺激因子1受体信号通路，Ki20227是一种高度选择性集落刺激因子1受体抑制剂。既往研究发现Ki20227可改变小胶质细胞的形态，然而其对缺血性脑卒中进展中小胶质细胞的作用仍不清楚。实验以大脑中动脉闭塞诱发的局灶性脑缺血损伤雄性C57BL/6小鼠模型为研究对象，连续3d灌胃3 mg/g的Ki20227。（1）发现模型小鼠脑梗死组织周围中Iba1 离子钙结合衔接分子1/BrdU双阳性细胞数量减少，脑水肿程度增加，神经功能障碍程度加重，梗死体积增加，加剧梗死周围尼氏小体减少；（2）模型小鼠脑梗死周围TUNEL阳性细胞数量增加， Bax和cleaved caspase-3表达水平上调， Bcl-2表达水平下调，1炎症反应和氧化应激相关的因子表达增加；（3）结果说明，Ki20227阻断了小胶质细胞的增殖，加重大脑中动脉短暂性脑缺血模型缺血/再灌注损伤的病理进程。实验于2020年3月6日经兰州大学第二医院动物伦理委员会批准（批准号D2020-68）。

https://orcid.org/0000-0002-1896-8031 (Bo-Ru Hou)

关键词: 缺血再灌注, 短暂性大脑中动脉阻塞, 集落刺激因子1受体, Ki20227, 细胞凋亡, 炎症反应, 氧化应激, 小胶质细胞

Abstract: The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

Key words: apoptosis, colony-stimulating factor-1 receptor, inflammatory response, ischemia/reperfusion, Ki20227, microglia, oxidative stress, transient middle cerebral artery occlusion