HMGB1-TLR4信号轴在大鼠心肌缺血再灌注损伤中的作用及机制研究  

The role and mechanism of HMGB1-TLR4 signaling axis in rat myocardial ischemia-reperfusion injury

作　　者：田立群[1] 张妍 冯莹[1] 余志华[1] 王代宗 易春峰 TIAN Li-qun;ZHANG Yan;FENG Ying;YU Zhi-hua;WANG Dai-zong;YI Chun-feng(Department of Cardiovascular Medicine,Wuhan First Hospital,Wuhan 430000,China)

机构地区：[1]武汉市第一医院心血管内科,武汉430000

出　　处：《现代免疫学》2022年第1期58-63,共6页Current Immunology

基　　金：武汉市卫计委基金(WX18D53)。

摘　　要：为探究高迁移率族蛋白1-Toll样受体4(high mobility group box 1-Toll-like receptor 4, HMGB1-TLR4)信号轴在大鼠心肌缺血再灌注损伤(ischemia-reperfusion injury, IRI)中的作用及可能机制,按随机数字表法将25只雄性SD大鼠分为对照组、模型组、假手术组、HMGB1阻滞组和TLR4阻滞组共5组,每组5只。采用心电图鉴定模型构建是否成功;H-E染色评估心肌组织炎症细胞浸润情况;TUNEL染色评估心肌细胞凋亡情况;免疫组织化学法评估心肌组织HMGB1、TLR4、TNF-α、IL-1β等炎症通路分子表达变化;ELISA检测大鼠外周血TNF-α、IL-17A、IL-6和IL-1β等分子浓度。结果显示,与对照组相比,假手术组中各信号通路分子表达量无显著差异(均P>0.05);与假手术组相比,模型组心肌组织呈局灶性溶解,炎症细胞浸润明显,心肌细胞凋亡率显著升高(P<0.01,P=0.000),HMGB1、TLR4、TNF-α、IL-1β蛋白表达量显著增加(P<0.01,P=0.000),大鼠外周血中TNF-α、IL-17A、IL-6和IL-1β浓度显著升高(P<0.01,P=0.000);与模型组相比,HMGB1阻滞组和TLR4阻滞组炎症细胞浸润减少,心肌细胞凋亡率显著降低(P<0.01,P=0.000),TNF-α、IL-17A、IL-6和IL-1β浓度显著减少(P<0.01,P=0.000)。综上,大鼠心肌IRI模型心肌组织中HMGB1-TLR4信号通路分子表达升高,并通过上调炎性因子的表达促进细胞凋亡。This study aimed to investigate the effect and mechanism of the high mobility group box 1-Toll-like receptor 4(HMGB1-TLR4) signaling axis in myocardial ischemia-reperfusion injury(IRI). Twenty-five male SD rats were divided into five groups(n=5 per group): the control, model, sham operation, HMGB1 blocked and TLR4 blocked group. Electrocardiography was performed to determine whether the model was successfully constructed. H-E staining was performed to evaluate the inflammatory infiltration in myocardial tissue. TUNEL staining was performed to detect the apoptosis of myocardiocytes. Expressions of HMGB1, TLR4, TNF-α, and IL-1β in the myocardial tissue were evaluated by immunohistochemistry. The concentrations of TNF-α, IL-17 A, IL-6, and IL-1β in peripheral blood were determined by ELISA. Compared with the normal group, there was no significant difference in the expression of any signaling pathway factor in the sham operation group(all P>0.05). Compared with the sham operation group, the myocardium of the model group was focally lysed in addition to significant inflammatory cell infiltration, and the apoptosis of myocardiocytes was more severe(P<0.01, P=0.000), and the protein expressions of HMGB1, TLR4, TNF-α, and IL-1β increased significantly(all P<0.01, P=0.000). The concentrations of TNF-α, IL-17 A, IL-6, and IL-1β in the peripheral blood of rats were significantly increased(all P<0.01, P=0.000). Compared with the model group, the infiltration of inflammatory cells in the HMGB1 blocked and TLR4 blocked groups was alleviated, cardiomyocyte apoptosis was suppressed(all P<0.01, P=0.000), and the concentrations of TNF-α, IL-17 A, IL-6, and IL-1β decreased significantly(all P<0.01, P=0.000). In conclusion, the above findings suggest that the HMGB1-TLR4 signaling axis is up-regulated in myocardial IRI model rats, and the expressions of inflammatory factors are increased resulting in increased apoptosis of myocardiocytes.

关 键 词：心肌缺血再灌注 炎症 高迁移率族蛋白1 TOLL样受体4 

分 类 号：R542.2[医药卫生—心血管疾病]