1. Moderate Hyperkalemia Regulates Autophagy to Reduce Cerebral Ischemia-Reperfusion Injury in a CA/CPR Rat Model.
- Author
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Wang, Xiaoqin, Tian, Xinyue, Shen, Haiying, Zhang, Xiaohua, Xie, Lu, and Chen, Menghua
- Subjects
REPERFUSION injury ,AUTOPHAGY ,ANIMAL disease models ,HYPERKALEMIA ,TRANSMISSION electron microscopy - Abstract
Background: Cerebral ischemia-reperfusion injury (CIRI) can cause irreversible brain damage and autophagy has been implicated in the pathophysiology. Increasing serum potassium (K
+ ) levels reduces CIRI, but the relationship between its protective mechanism and autophagy is unclear. In this study, we aimed to find the optimal degree of raising serum (K+ ) and to investigate the relationship between high (K+ ) and autophagy and the underlying mechanisms in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) rat model. Methods: Sprague Dawley (SD) rats were divided into four groups: S group, N group, P group, and Q group. The rats S group and N group were administered saline. The rats P group and Q group were administered 640 mg/kg of potassium chloride (KCl) continuously pumped at 4 mL/h (21.3 mg/(kg·min) and divided according to the electrocardiogram (ECG) changes during the administration of KCl. After 24-h of resuscitation, neural damage was assessed by measuring neurological deficit score (NDS), oxidative stress markers, and pathological staining of the cerebral cortex. The level of autophagy and the expression of mTOR-ULK1-Beclin1 pathway-related proteins were evaluated using transmission electron microscopy (TEM), immunostaining, and western blotting. Results: Our results revealed that high (K+ ) improved NDS and decreased the oxidative stress markers. The autophagosomes, autolysosomes, and lysosomes were decreased following treatment KCl. Furthermore, the levels of micro-tubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ, Unc-51-like kinase 1 (ULK1), and Beclin1 were decreased, whereas mTOR expression was increased in the cortex. Conclusion: The results demonstrated that moderate hyperkalemia could alleviate autophagy after CIRI via regulating the mTOR-ULK1-Beclin1 pathway. [ABSTRACT FROM AUTHOR]- Published
- 2023
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