右美托咪定对大鼠心肌缺血再灌注损伤程度、炎性因子及Toll样受体4/核因子кB信号通路的影响研究  

Impact of Dexmedetomidine on Severity of Myocardial Ischemia Reperfusion Injury,Inflammatory Cytokines and TLR4/NF-κB Signaling Pathway in Rats

作　　者：任小鹏[1] 孙春喜[1] 李建成 高彦霞 潘龙飞 REN Xiaopeng;SUN Chunxi;LI Jiancheng;GAO Yanxia;PAN Longfei(The First Ward of Department of Cardiovascular Medicine,Shangluo Central Hospital,Shangluo 726000,China;Department of Emergency Medicine,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]陕西省商洛市中心医院心血管内科一病区,726000 [2]西安交通大学第二附属医院急诊科,陕西省西安市710004

出　　处：《实用心脑肺血管病杂志》2019年第12期63-67,共5页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：陕西省科学技术研究发展计划项目(2016YFJH2-05);西安交通大学第二附属医院科研基金青年项目[YJ(QN)201523]

摘　　要：背景右美托咪定主要通过Toll样受体4/核因子κB(TLR4/NF-κB)信号通路而发挥炎症调节作用,但目前关于其对心肌缺血再灌注损伤的保护机制研究报道较少。目的探讨右美托咪定对大鼠心肌缺血再灌注损伤程度、炎性因子、TLR4/NF-κB信号通路的影响。方法 2018年2-12月,将大鼠源性H9C2心肌细胞随机分为对照组、心肌细胞损伤组、预处理组。对照组心肌细胞进行常规培养,心肌细胞损伤组心肌细胞建立缺血再灌注损伤模型,预处理组心肌细胞给予右美托咪定,后建立缺血再灌注损伤模型。观察心肌细胞形态学变化,比较三组心肌细胞生存率、炎性因子[包括肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、白介素1β(IL-1β)]mRNA相对表达量及TLR4、NF-κB蛋白相对表达量。结果 (1)对照组心肌细胞排列整齐,细胞膜表明光滑;心肌细胞损伤组心肌细胞形态不一,存在心肌细胞凋亡、脱落、漂浮现象;预处理组心肌细胞由缺氧-复氧损伤引起的形态学改变减轻。(2)心肌细胞损伤组、预处理组心肌细胞存活率均低于对照组,而预处理组心肌细胞存活率高于心肌细胞损伤组(P<0.05)。(3)心肌细胞损伤组、预处理组心肌细胞TNF-α、IL-6、IL-1βmRNA相对表达量均高于对照组,而预处理组心肌细胞TNF-α、IL-6、IL-1βmRNA相对表达量低于心肌细胞损伤组(P<0.05)。(4)心肌细胞损伤组、预处理组心肌细胞TLR4、NF-κB蛋白相对表达量高于对照组,而预处理组心肌细胞TLR4、NF-κB蛋白相对表达量低于心肌细胞损伤组(P<0.05)。结论右美托咪定能有效改善大鼠缺血再灌注损伤心肌细胞存活率,减轻炎性反应,其可能通过下调心肌细胞TLR4/NF-κB信号通路活性而减轻大鼠心肌缺血再灌注损伤程度。Background Dexmedetomidine may regulate inflammation through TLR4/NF-κB signaling pathway,but there is few reports about its protective mechanism in myocardial ischemia reperfusion injury. Objective To explore the impact of dexmedetomidine on severity of myocardial ischemia reperfusion injury,inflammatory cytokines and TLR4/NF-κB signaling pathway in rats. Methods This experiment was conducted from February to December 2018. Rat derived H9C2 myocardial cells were randomly divided into control group,myocardial cell injury group and pretreatment group. Myocardial cells in control group were cultured routinely,myocardial cells in myocardial cell injury group were prepared for myocardial ischemia reperfusion injury model,while myocardial cells in pretreatment group were treated with dexmedetomidine before the preparation of myocardial ischemia reperfusion injury model. Morphological changes of myocardial cells were observed,moreover comparison of survival rate,relative mRNA expression quantity of inflammatory cytokines(including TNF-α,IL-6 and IL-1β),relative protein expression quantity of TLR4 and NF-κB was conducted in the three groups. Results(1)Myocardial cells in control group were well-aligned with smooth cell membrane;myocardial cells in myocardial cell injury group were different in morphology,with apoptosis,exfoliates and floats;morphological changes of myocardial cells caused by ischemia-reperfusion injury in pretreatment group were alleviated.(2)Survival rate in myocardial cell injury group and pretreatment group was statistically significantly lower than that in control group,while survival rate in pretreatment group was statistically significantly higher than that in myocardial cell injury group(P<0.05).(3)Relative mRNA expression quantity of TNF-α,IL-1β and IL-6 in myocardial cell injury group and pretreatment group was statistically significantly higher than that in control group,respectively,while relative mRNA expression quantity of TNF-α,IL-1β and IL-6 mRNA in pretreatment group was statist

关 键 词：心肌再灌注损伤 右美托咪定 大鼠 心肌细胞 TLR4/NF-κB信号通路 炎性反应 

分 类 号：R542.2[医药卫生—心血管疾病]