Protective effects of α-ketoglutarate dehydrogenase complex in adaptive reperfusion following ischemia stroke
10.12092/j.issn.1009-2501.2020.09.001
- VernacularTitle: α-酮戊二酸脱氢酶复合物在缺血性脑卒中后的适应性再灌注中的保护作用研究
- Author:
Zuoqian CHEN
1
Author Information
1. Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University
- Publication Type:Journal Article
- Keywords:
Adaptive reperfusion;
Apoptosis;
Ischemia stroke;
Α-ketoglutarate dehydrogenase complex
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(9):961-967
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate whether α-ketoglutarate dehydrogenase complex (α-KGDHC) has protective effects on adaptive reperfusion after ischemic stroke in rats, and whether its mechanism is related to inhibition of apoptotic pathways. METHODS: A model of middle cerebral artery occlusion (MCAO) ischemia/reperfusion (I/R) was established, and the volume of cerebral infarction was assessed by TTC staining following computer analysis. The α-KGDHC activity was detected based on chemical reaction, to evaluate the change trend of α-KGDHC activity with cerebral ischemia time, and compare the difference between normal reperfusion group and adaptive reperfusion group; treatment of B35 and SH-SY5Y with CoCl2 to mimic cell hypoxia, and inhibition of α-KGDHC activity with E1K siRNA to detect the expression of apoptosis-related proteins Bcl-2/Bax/Caspase 3 by Western blot. RESULTS: In vivo experiments: In MCAO model, adaptive reperfusion further reduced cerebral infarction volume compared with normal reperfusion (P<0.05), and the expression of Caspase 3 was the lowest; α-KGDHC activity in cerebral cortex and hippocampal brain tissue decreased as ischemic time prolonged (P<0.05), and adaptive reperfusion inhibited the rate of decrease in α-KGDHC activity (P<0.05). In vitro experiments: Inhibiting α-KGDHC activity by interfering E1K expression led to downregulation of Bcl-2 (P<0.05) and upregulation of Bax (P<0.05) and Caspase 3 (P<0.05). CONCLUSION: α-KGDHC is an important factor in the protection of adaptive reperfusion after cerebral ischemia, and it may exert protective effect by inhibiting the activation of apoptotic pathways.
