Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.
10.3724/zdxbyxb-2021-0164
- Author:
Ran ZHANG
1
;
Yun LIU
1
;
Cui ZHANG
1
;
Mengyao MA
1
;
Shu LI
1
;
Yun HONG
1
Author Information
1. Clinical Colloge of Wannan Medical College.
- Publication Type:Journal Article
- Keywords:
Adenosine diphosphate;
Adenosine triphosphate;
Energy metabolism;
Hypoxia-inducible factor-1α;
Ischemia reperfusion;
SD rat;
Salt-inducible kinase 2
- MeSH:
Animals;
Brain Ischemia;
Energy Metabolism;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*;
Infarction, Middle Cerebral Artery;
Male;
Protein-Serine-Threonine Kinases;
Rats;
Rats, Sprague-Dawley;
Reperfusion;
Reperfusion Injury
- From:
Journal of Zhejiang University. Medical sciences
2021;50(3):352-360
- CountryChina
- Language:English
-
Abstract:
To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.
