右侧颈交感干离断对大鼠心肌梗死后炎症反应的抑制作用及对HMGB1/TLR4/NF-κB通路的影响  

Inhibitory effects of right cervical sympathetic trunk transection on inflammatory response after acute myocardial infarction in rats and its influence on HMGB1/TLR4/NF-κB signaling pathway

作　　者：何姗姗 余娅[1] 高进[1] 赖增燕 陈萍[1] HE Shan-shan;YU Ya;GAO Jin;LAI Zeng-yan;CHEN Ping(Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016

出　　处：《中国病理生理杂志》2018年第3期403-409,共7页Chinese Journal of Pathophysiology

基　　金：重庆市渝中区科技计划项目(No.20130116);重庆市卫生部国家临床重点专科建设项目[财社(2011)170号];重庆市医学重点学科资助项目[渝卫科教(2007)2号]

摘　　要：目的:观察右侧颈交感干离断(TCST)对大鼠心肌梗死后炎症反应的抑制作用及高迁移率族蛋白B1(HMGB1)的表达和TLR4/NF-κB信号通路的影响。方法:结扎左冠状动脉前降支制备急性心肌梗死(acute myocardial infarction,AMI)模型,将造模成功的大鼠随机分为心肌梗死(MI)组和心肌梗死+右侧颈交感干离断(MI+TCST)组,MI+TCST组在左冠状动脉前降支结扎后立即离断右侧颈交感神经干。MI组和MI+TCST组分别按模型制备及干预后1、3、7、14和28 d分为5个亚组,另设假手术(sham)组,只穿线不结扎,每组8只。建模后4周,超声心动图检测大鼠心脏功能,然后处死大鼠,取心脏计算心脏肥厚指数,并取梗死周围心肌组织采用HE染色观察心肌病理形态改变。Real-time PCR法检测不同时点梗死边缘区HMGB1、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的m RNA表达。Western blot分析MI后不同时点梗死边缘区HMGB1和TLR4蛋白的表达变化,并进一步分析右侧TCST对HMGB1和TLR4/NF-κB信号通路蛋白表达的影响。结果:与MI组比较,MI+TCST组左心室射血分数(LVEF)和左心室短轴缩短分数(LVFS)显著升高(P<0.05),左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)和心脏肥厚指数显著降低(P<0.05),梗死边缘区各时点HMGB1、TNF-α和IL-6的m RNA表达水平显著降低(P<0.05)。Western blot检测结果显示,与sham组比较,HMGB1蛋白的表达在MI后3 d开始升高,并于7 d达到高峰,之后逐渐下降,28 d时仍明显高于假手术组(P<0.05);TLR4蛋白的表达变化与HMGB1一致。进一步研究发现右侧TCST可显著降低心肌组织HMGB1和TLR4/NF-κB信号通路蛋白的表达(P<0.05)。结论:右侧颈交感干离断可改善MI后心室重构,发挥保护心功能的作用,其机制可能与其抑制HMGB1/TLR4/NF-κB信号通路,减轻炎症反应有关。AIM:To observe the effects of transection of right cervical sympathetic trunk(TCST)on inflammatory response and expression of high mobility group box1(HMGB1)and TLR4/NF-κB signaling pathway in the rats after acute myocardial infarction(AMI).METHODS:AMI model was established by ligation of left anterior descending coronary artery in SD rats,then the model rats were randomly divided into MI group and MI+TCST group.MI+TCST model was performed by transection of right cervical sympathetic trunk after left anterior descending coronary artery ligation.The rats in MI group and MI+TCST group were divided into1,3,7,14and28d subgroups,and another sham operation group threading without ligation,with8rats in above each group.After modeling for4weeks,the cardiac function was measured by echocardiography.All rats were killed to harvest the hearts for mesuring cardiac hypertrophy index.The myocardial tissue close to infarction was observed with HE staining.The relative mRNA expression levels of HMGB1,tumor necrosis factorα(TNF-α)and interleukin(IL)-6at different time points were detected by real-time PCR.The protein expression of HMGB1and TLR4at different time points after AMI was determined by Western blot.The effect of transection of right cervical sympathetic trunk on the expressions of HMGB1and TLR4/NF-κB signaling pathway was also analyzed.RESULTS:Compared with the MI group,left ventricular ejection fraction(LVEF)and left ventricular shorterning fraction(LVFS)were significantly higher(P<0.05),left ventricular end-diastole dimension(LVEDd),left ventricular end-systole dimension(LVESd)and cardiac hypertrophy index were significantly lower(P<0.05),and the mRNA levels of HMGB1,TNF-αand IL-6decreased significantly in MI+TCST group(P<0.05).Western blot results revealed that the protein expression level of HMGB1increased in the infarct border zone at3d,and reached its peak at7d,then gradually decreased,and at28d after MI in MI group was still significantly higher than that in sham group(P<0.05).The protein expression of TLR4w

关 键 词：心肌梗死 心室重构 颈交感干离断 炎症反应 高迁移率族蛋白B1 TLR4/NF-κB信号通路 

分 类 号：R542.22[医药卫生—心血管疾病] R363.2[医药卫生—内科学]