The Intensive Care Unit, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
The Department of Physiology, School of Pre-Clinical Science, Guangxi Medical University, Nanning, China.
J Neurosci Res. 2019 Oct;97(10):1253-1265. doi: 10.1002/jnr.24483. Epub 2019 Jun 25.
Imbalances between cellular K efflux and influx are considered to be involved in cerebral ischemia-reperfusion (I/R) injury. High-potassium pretreatment alleviates this injury, but the underlying molecular mechanism is unclear. In this study, we sought to investigate whether high-potassium preconditioning enhances cerebral tolerance to I/R injury through an anti-apoptotic mechanism. Adult male Sprague-Dawley rats were randomly divided into four groups (n = 40/group): a sham-operated group, normal saline group (3.2 ml/kg saline, intravenous (IV)), and low-dose and high-dose potassium chloride (KCl) groups (40 and 80 mg/kg KCl solution, IV, respectively). Subsequently, the rats underwent 90 min of middle cerebral artery occlusion (MCAO) followed by 24 hr of reperfusion (MCAO/R). Neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining, and TUNEL assay were used to assess neural injury. The expression of apoptotic proteins, brain potassium levels, mitochondrial function and oxidative stress were detected to explore the potential mechanism. After 24 hr of reperfusion, in both KCl treatment groups, neurological deficits and the cerebral infarct volume were reduced, and the apoptosis index of neurons was decreased. Furthermore, high-potassium preconditioning increased brain K , adenosine triphosphate (ATP), cytochrome c oxidase (COX) levels, reduced malondialdehyde level, improved Na /K -ATPase, succinic dehydrogenase and superoxide dismutase activities, upregulated anti-apoptotic protein expression, and downregulated pro-apoptotic protein expression. This study suggests that high-potassium preconditioning enhanced cerebral tolerance to I/R injury in a rat MCAO/R model. The protective mechanism may involve apoptosis inhibition via preservation of intracellular K and improvement of mitochondrial function.
细胞内钾离子流出和流入的失衡被认为与脑缺血再灌注（I/R）损伤有关。高钾预处理可以减轻这种损伤，但潜在的分子机制尚不清楚。在本研究中，我们试图探讨高钾预处理是否通过抗细胞凋亡机制增强脑对 I/R 损伤的耐受。将成年雄性 Sprague-Dawley 大鼠随机分为四组（n=40/组）：假手术组、生理盐水组（3.2ml/kg 生理盐水，静脉注射（IV））和低剂量及高剂量氯化钾（KCl）组（分别给予 40 和 80mg/kg KCl 溶液，IV）。随后，大鼠进行 90min 大脑中动脉闭塞（MCAO），再灌注 24h（MCAO/R）。神经功能缺损评分、2,3,5-三苯基四氮唑氯（TTC）染色、苏木精和伊红染色以及 TUNEL 检测用于评估神经损伤。检测凋亡蛋白表达、脑钾水平、线粒体功能和氧化应激，以探讨潜在的机制。再灌注 24h 后，在 KCl 处理组中，神经功能缺损和脑梗死体积减少，神经元凋亡指数降低。此外，高钾预处理增加脑 K+、三磷酸腺苷（ATP）、细胞色素 c 氧化酶（COX）水平，降低丙二醛水平，改善钠/钾-ATP 酶、琥珀酸脱氢酶和超氧化物歧化酶活性，上调抗凋亡蛋白表达，下调促凋亡蛋白表达。本研究表明，高钾预处理增强了大鼠 MCAO/R 模型脑对 I/R 损伤的耐受。保护机制可能涉及通过维持细胞内 K+和改善线粒体功能来抑制细胞凋亡。
