Zhao Yunlong, Xue Yan, Liu Zehan, Ren Shuai, Guan Xiangchen, Li Ming, Zhao Xin, Song Yang, Ren Xiaoping
Hand and Microsurgery Center, The Second Affiliated Hospital of Harbin Medical University.
State-Province Key Laboratories of Biomedicine-Pharmaceutics.
Neuroreport. 2019 Jun 12;30(9):664-670. doi: 10.1097/WNR.0000000000001257.
Remote ischemia preconditioning (RIPC) is a convenient and effective method for alleviating cerebral ischemia-reperfusion injury (CIRI). However, to date, the underlying mechanism has not been fully elucidated. The aim of this research was to explore the protective mechanism of RIPC on the brain after CIRI. Four groups of rats were included in this experiment: the sham group, the middle cerebral artery occlusion (MCAO) group, the RIPC group, and the AG490 group. As an inhibitor of Janus kinase 2 (JAK2), AG490 was used after MCAO in the AG490 group to explore the role of JAK2/signal transducers and activators of transcription 3 (STAT3) after CIRI. Brain tissue was collected for evaluation after 2 h of ischemia and 24 h of reperfusion. ELISA for interleukin (IL)-6, IL-1β and tumor necrosis factor-α, western blot for phosphorylated-JAK2 and phosphorylated-STAT3, the neurological severity score and Longa scoring system for neurological deficit evaluation, triphenyltetrazolium chloride staining for cerebral infarction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining for apoptotic cells in the brain tissue were performed. Neurological function in the RIPC group was notably better than that in the MCAO group. There were smaller infarction sizes and fewer apoptotic cells in the ischemic area in the RIPC group than in the MCAO group. In the RIPC group, the expression levels of IL-1β, tumor necrosis factor-α, IL-6, and phosphorylated-JAK2 and phosphorylated-STAT3 were significantly lower than those in the MCAO group. The findings in the RIPC and AG490 groups were similar. The inflammatory response and apoptosis are two important processes involved in brain dysfunction after CIRI. The JAK2/STAT3 signaling pathway has an underlying relationship with these two processes. These findings suggest that RIPC can alleviate the damage to brain tissue by CIRI by regulating the JAK2/STAT3 signaling pathway negatively.
远程缺血预处理（RIPC）是一种减轻脑缺血再灌注损伤（CIRI）的便捷有效方法。然而，迄今为止，其潜在机制尚未完全阐明。本研究的目的是探讨RIPC对CIRI后脑组织的保护机制。本实验纳入四组大鼠：假手术组、大脑中动脉闭塞（MCAO）组、RIPC组和AG490组。作为Janus激酶2（JAK2）的抑制剂，AG490在MCAO后用于AG490组，以探讨CIRI后JAK2/信号转导子和转录激活子3（STAT3）的作用。在缺血2小时和再灌注24小时后收集脑组织进行评估。进行白细胞介素（IL）-6、IL-1β和肿瘤坏死因子-α的酶联免疫吸附测定（ELISA），磷酸化JAK2和磷酸化STAT3的蛋白质免疫印迹法，用于神经功能缺损评估的神经严重程度评分和Longa评分系统，用于脑梗死的氯化三苯基四氮唑染色，以及用于脑组织中凋亡细胞的末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色。RIPC组的神经功能明显优于MCAO组。与MCAO组相比，RIPC组缺血区域的梗死面积更小，凋亡细胞更少。在RIPC组中，IL-1β、肿瘤坏死因子-α、IL-6以及磷酸化JAK2和磷酸化STAT3的表达水平明显低于MCAO组。RIPC组和AG490组的结果相似。炎症反应和细胞凋亡是CIRI后脑功能障碍涉及的两个重要过程。JAK2/STAT3信号通路与这两个过程存在潜在关系。这些发现表明，RIPC可通过负向调节JAK2/STAT3信号通路减轻CIRI对脑组织的损伤。
