低剂量艾司氯胺酮通过TLR4/MyD88/NF-κB通路减轻肢体缺血再灌注损伤  

Low dose of esketamine alleviates limb ischemia reperfusion injury through TLR4/MyD88/NF-κB pathway

作　　者：袁培根[1] 杨晓丹 单鸳露[1] 薛彬彬[1] 叶玉柱 林丽娜[1] YUAN Peigen;YANG Xiaodan;SHAN Yuanlu;XUE Binbin;YE Yuzhu;LIN Lina(Department of Anesthesiology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,浙江温州325000

出　　处：《中国现代医生》2023年第31期82-85,89,共5页China Modern Doctor

基　　金：浙江省温州市科技计划项目(Y2020777)。

摘　　要：目的探讨Toll样受体4(Toll-like receptor 4,TLR4)/髓样分化初级反应基因88(myeloid differentiation primary response gene 88,MyD88)/核因子-κB(nuclear factor-κB,NF-κB)通路在低剂量艾司氯胺酮预处理的肢体缺血再灌注损伤中的作用。方法将28只大鼠分为对照组、模型组、实验1组(艾司氯胺酮,5mg/kg)、实验2组(艾司氯胺酮,10mg/kg),每组各7只。实验组大鼠腹腔注射艾司氯胺酮,其余两组同样方法给予生理盐水,造模成功后取血清测定白细胞介素(interleukin,IL)-6、IL-1和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量;取骨骼肌测定湿/干重比值,测定TLR4、MyD88基因表达水平和NF-κB蛋白含量,病理切片观察骨骼肌改变。结果与对照组相比,模型组湿/干重比值、IL-6、IL-1、TNF-α、TLR4 mRNA、MyD88 mRNA及NF-κB蛋白均显著升高(P<0.05);与模型组相比,实验1组和实验2组的上述各项指标均显著降低(P<0.05);而实验1组和实验2组的上述各项指标比较差异均无统计学意义(P>0.05)。结论艾司氯胺酮可通过TLR4/MyD88/NF-κB通路降低相关炎症因子表达,从而减轻肢体缺血再灌注损伤,且低剂量的艾司氯胺酮即可起到抗炎保护作用。Objective To investigate the role of Toll-like receptor 4(TLR4)/myeloid differentiation primary response gene 88(MyD88)/nuclear factor-κB(NF-κB)pathway in limb ischemia reperfusion injury pretreated with low dose esketamine.Methods Twenty-eight rats were divided into control group,model group,experiment group 1(esketamine,5mg/kg)and experiment group 2(esketamine,10mg/kg),with 7 rats in each group.Rats in experimental group were intraperitoneally injected esketamine,and the other two groups were given normal saline in the same way.After successful modeling,serum levels of interleukin(IL)-6,IL-1,and tumor necrosis factor-α(TNF-α)were collected and determined.The wet/dry weight ratio of skeletal muscle was determined,the expression level of TLR4,MyD88 gene and the content of NF-κB protein were determined,and the changes of skeletal muscle were observed in pathological sections.Results Compared with control group,the wet/dry weight ratio,IL-6,IL-1,TNF-α,TLR4 mRNA,MyD88 mRNA and NF-κB protein were significantly increased in model group(P<0.05).Compared with model group,the above indexes in experiment group 1 and experiment group 2 were significantly reduced(P<0.05).The comparison of the above indexes between experiment group 1 and experiment group 2 were no significant difference(P>0.05).Conclusion Esketamine can reduce the expression of related inflammatory factors through TLR4/MyD88/NF-κB pathway,thereby alleviating limb ischemia reperfusion injury,and low dose esketamine can play an anti-inflammatory protective effect.

关 键 词：缺血再灌注损伤 炎症反应 TLR4/NF-κB信号通路 艾司氯胺酮 

分 类 号：R364[医药卫生—病理学]