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

Abstract

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. Keywords: Hypoxia inducible factor 1α; Bcl-2/adenovirus E1B 19-kDa interacting protein 3; interleukin-4; cerebral ischemia reperfusion injury.