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

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. 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. 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). IL-4 reduces apoptosis and oxidative stress through activating the HIF-1α/BNIP3 pathway, thereby alleviating mouse CIRI.