缺氧诱导因子 1α/Bcl-2/腺病毒 E1B 19-kDa 相互作用蛋白 3 在白细胞介素-4 减轻小鼠脑缺血再灌注损伤中的作用。
Role of hypoxia inducible factor 1α/Bcl-2/adenovirus E1B 19-kDa interacting protein 3 in alleviating effect of interleukin-4 on cerebral ischemia reperfusion injury in mice.
机构信息
Department of Geriatrics, Daqing Oilfield General Hospital, Daqing 163001, Heilongjiang Province, China.
Department of Neurology, Daqing Oilfield General Hospital, Daqing 163001, Heilongjiang Province, China.
出版信息
Afr Health Sci. 2022 Sep;22(3):369-374. doi: 10.4314/ahs.v22i3.39.
BACKGROUND
Cerebral ischemia reperfusion injury (CIRI) is the pathophysiological basis of various cerebrovascular diseases. The aim of this study was to explore the role of HIF-1α/BNIP3 in the alleviating effect of IL-4 on CIRI in mice.
METHODOLOGY
Mice were randomly divided into sham operation (Sham), ischemia reperfusion (IR), IL-4, HIF-1α inhibitor 2ME2 and IL-4+2ME2 groups. Middle cerebral artery occlusion model was established. After 24-h reperfusion, neurologic deficit score (NDS) was given. Cerebral infarction volume and brain water content were measured by 2,3,5-triphenyltetrazolium chloride staining and dry-wet weights, respectively. Apoptosis was detected by TUNEL staining. SOD, MDA and ROS levels, and HIF-1α, BNIP3, LC3II and Beclin-1 expressions were detected through colorimetry and Western blotting, respectively.
RESULTS
Compared with IR group, NDS, cerebral infarction volume, brain water content, apoptosis rate, and MDA and ROS levels decreased, while SOD, HIF-1α, BNIP3, LC3-II and Beclin-1 levels increased in IL-4 group (P<0.05). 2ME2 and IL-4+2ME2 groups had decreased NDS, cerebral infarction volume, brain water content, apoptosis rate and MDA, ROS, HIF-1α, BNIP3, LC3-II and Beclin-1 levels, but increased SOD level compared with those of IL-4 group (P<0.05).
CONCLUSION
IL-4 reduces apoptosis and oxidative stress through activating the HIF-1α/BNIP3 pathway, thereby alleviating mouse CIRI.
背景
脑缺血再灌注损伤（CIRI）是各种脑血管疾病的病理生理基础。本研究旨在探讨 HIF-1α/BNIP3 在 IL-4 减轻小鼠 CIRI 中的作用。
方法
将小鼠随机分为假手术（Sham）、缺血再灌注（IR）、IL-4、HIF-1α 抑制剂 2ME2 和 IL-4+2ME2 组。建立大脑中动脉闭塞模型。再灌注 24 小时后，给予神经功能缺损评分（NDS）。通过 2,3,5-三苯基四氮唑氯化物染色和干湿重法测量脑梗死体积和脑水含量。通过 TUNEL 染色检测细胞凋亡。通过比色法和 Western blot 法分别检测 SOD、MDA 和 ROS 水平以及 HIF-1α、BNIP3、LC3II 和 Beclin-1 的表达。
结果
与 IR 组相比，IL-4 组 NDS、脑梗死体积、脑水含量、细胞凋亡率以及 MDA 和 ROS 水平降低，SOD、HIF-1α、BNIP3、LC3-II 和 Beclin-1 水平升高（P<0.05）。2ME2 和 IL-4+2ME2 组与 IL-4 组相比，NDS、脑梗死体积、脑水含量、细胞凋亡率及 MDA、ROS、HIF-1α、BNIP3、LC3-II 和 Beclin-1 水平降低，SOD 水平升高（P<0.05）。
结论
IL-4 通过激活 HIF-1α/BNIP3 通路减少细胞凋亡和氧化应激，从而减轻小鼠 CIRI。
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