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Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.

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.
AuthorsRan Zhang, Yun Liu, Cui Zhang, Mengyao Ma, Shu Li, Yun Hong
JournalZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences (Zhejiang Da Xue Xue Bao Yi Xue Ban) Vol. 50 Issue 3 Pg. 352-360 (Jun 25 2021) ISSN: 1008-9292 [Print] China
PMID34402252 (Publication Type: Journal Article)
Chemical References
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Protein Serine-Threonine Kinases
  • SIK2 protein, rat
Topics
  • 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

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