Mechanism of moderately elevated serum potassium in alleviating cerebral ischemia-reperfusion injury in rats via the Ca2+/CaMKⅡ/Caspase-3 signaling pathway
FANG Wei
LI Nuo
GAN Weini
QIN Sina
LU Junyu
CHEN Menghua
HUANG Ying
YANG Yegui
Abstract：Objective To investigate whether a moderate elevation of serum potassium exerts neuroprotective effects in the rat models with cerebral ischemia-reperfusion injury(CIRI)by modulating the Ca²⁺/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/Caspase-3 signaling pathway.Methods Ninety-six Sprague-Dawley(SD)rats were assigned into four groups(n=24 per group)using a random number table method:the sham-operated group(Sham group),the model group,the high-dose potassium chloride group(HD group),and the low-dose potassium chloride group(LD group),re-spectively.The CIRI models were established by inducing middle cerebral artery occlusion(MCAO)using the intralumi-nal filament technique.After 90 minutes of occlusion,the filament was withdrawn to restore cerebral blood flow,thereby achieving reperfusion.In the Sham group,only vascular dissection was performed.At the onset of reperfusion,rats in the HD,LD,and model groups were administered an equal volume(3.2 mL/kg)of 2.5%potassium chloride solution(equiva-lent KCl dose:80 mg/kg),1.25%potassium chloride solution(equivalent KCl dose:40 mg/kg),and normal saline(0.9%NaCl),respectively,via intravenous injection into the internal jugular vein.After 24 hours,rats were sacrificed,and brain tissues were collected.TTC staining was used to observe the pathological changes and measure infarct volume.TUNEL staining was applied to assess neuronal apoptosis,and commercial kits were employed to determine K⁺ and Ca²⁺ lev-els.The expression levels of proteins associated with the calcium signaling pathway CaMKⅡ,its phosphorylated form at Thr-286/287(p-CaMKⅡ-Thr-286/287),as well as the apoptosis-related proteins B-cell lymphoma 2(Bcl-2),Bcl-2-as-sociated X protein(Bax),and cleaved Caspase-3(Cleaved-Caspase-3)were detected by Western blotting.Results In the model group,large pale infarct areas were observed in the brain tissues.Compared with the model group,both the LD and HD groups showed a reduction in the infarct area,with the HD group exhibiting a more significant decrease than the LD group.Compared with the Sham group,the model group exhibited a significantly larger cerebral infarct volume percent-age,a higher rate of neuronal apoptosis,a decreased concentration of K⁺ and an increased concentration of Ca²⁺ in the brain tissues.Furthermore,the protein expression levels of CaMKⅡ,p-CaMKⅡ-Thr-286/287,Bax,and Cleaved-Cas-pase-3 were significantly up-regulated,while the expression of Bcl-2 was down-regulated in the model group(all P<0.05).Compared with the model group,the HD group showed a significantly lower percentage of cerebral infarct volume,a reduced rate of neuronal apoptosis,an increased concentration of K⁺ and a decreased concentration of Ca²⁺ in the brain tissues.Furthermore,the protein expression levels of CaMKII,p-CaMKⅡ,Bax,and Cleaved-Caspase-3 were significant-ly down-regulated,while the expression of Bcl-2 was up-regulated in the HD group(all P<0.05).In the LD group,the brain tissue K⁺ concentration and Bcl-2 protein expression were significantly higher than those in the model group(both P<0.05).Conclusion The administration of a moderately elevated dose of potassium chloride to CIRI rats,at a tolerable level,may increase serum potassium,reduce intracellular calcium concentration,inhibit the Ca²⁺/CaMKⅡ/Caspase-3 signaling pathway,consequently decrease neuronal apoptosis,and exert a neuroprotective effect.
Keywords：cerebral ischemia-reperfusion injuryserum potassiumcalcium overloadcalcium ionCa²⁺/calmod-ulin-dependent protein kinase ⅡCaspase-3neuronal apoptosisrats
Publication Date：2026-02-25
Online Publishing Date：2026-03-19(First online date of this platform, not the publication date of the document)
Pages：6( 21-26 )