实用临床医药杂志2025，Vol.29Issue(16)：28-34,7.DOI:10.7619/jcmp.20245593
右美托咪定调控TLR4/NF-κB/NLRP3信号通路改善缺血性脑卒中模型大鼠认知功能的机制研究
Mechanism of dexmedetomidine in improving cognitive function in rats with ischemic stroke by modulating TLR4/NF-κB/NLRP3 signaling pathway
摘要
Abstract
Objective To investigate the effect of dexmedetomidine(DEX)on cognitive func-tion in rats with cerebral ischemic stroke(CIS)and analyze its potential underlying mechanisms.Methods A rat model of CIS was established using the middle cerebral artery occlusion(MCAO)method.The rats were randomly divided into sham-operation group,model group,low-dose DEX group(25 mg/kg DEX solution,administered by gavage),high-dose DEX group(50 mg/kg DEX solution,administered by gavage),and edaravone group(3.2 mg/kg edaravone solution,adminis-tered by gavage).After treatment,cognitive function was assessed using the neurological deficit score and the novel object recognition test.Brain infarction area and histopathological damage in brain tis-sue were detected using triphenyltetrazolium chloride(TTC)staining and hematoxylin and eosin(HE)staining,respectively.The expression of the microglial marker ionized calcium-binding adapter molecule 1(Iba-1)was analyzed using immunohistochemical staining.The levels of interleukin(IL)-6,IL-18,and IL-1β in brain tissue were measured using ELISA kits.The expression of proteins related to the toll-like receptor 4/nuclear factor KB/NOD-like receptor thermal protein do-main-containing protein 3(TLR4/NF-κB/NLRP3)signaling pathway was detected using western blot.Results Compared with the sham-operation group,the model group exhibited increased or enlarged neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,as well as a decreased novel object discrimination in-dex.Compared with the model group,the low-dose DEX,high-dose DEX,and edaravone groups showed decreased or shrinked neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,along with an increased novel object discrimination index.Compared with the low-dose DEX and edaravone groups,the high-dose DEX group demonstrated further decreases in neurological scores,brain in-farction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N-terminal domain(GSDMD-N),as well as an increased novel object discrimination index.The differences among the aforementioned groups were all statistically significant(P＜0.05).Conclusion DEX improves cognitive function in rats with CIS by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway,thereby suppressing neuronal pyroptosis and micro-glial activation and alleviating the inflammatory response.关键词
右美托咪定/缺血性脑卒中/神经元/细胞焦亡/认知功能/Toll样受体4/核因子κB/NOD样受体热蛋白结构域蛋白3/信号通路Key words
dexmedetomidine/cerebral ischemic stroke/neuron/pyroptosis/cognitive func-tion/toll-like receptor 4/nuclear factor κB/NOD-like receptor thermal protein domain-containing protein 3/signaling pathway分类
医药卫生引用本文复制引用
曹明,张剑波,马永圆..右美托咪定调控TLR4/NF-κB/NLRP3信号通路改善缺血性脑卒中模型大鼠认知功能的机制研究[J].实用临床医药杂志,2025,29(16):28-34,7.基金项目
广东省医学科学技术研究基金项目(A2024529) （A2024529）
