乔松素抑制TLR4/NF-κB/NLRP3信号通路对急性心肌梗死大鼠炎症损伤的影响  

Influences of Pinocembrin on inflammatory injury in rats with acute myocardial infarction by inhibiting TLR4/NF-κB/NLRP3 signaling pathway

作　　者：姚书霞 史璇 韩松 杨小蕾 王蕾 YAO Shuxia;SHI Xuan;HAN Song;YANG Xiaolei;WANG Lei(Department of Cardiology,the First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China;Department of Gastroenterology,the First Affili-ated Hospital of Jinzhou Medical University,Jinzhou 121000,China;Pathology Teaching and Research Office,School of Basic Medicine,Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]锦州医科大学附属第一医院心内科,锦州121000 [2]锦州医科大学附属第一医院消化科,锦州121000 [3]锦州医科大学基础医学院病理学教研室,锦州121000

出　　处：《中国免疫学杂志》2024年第12期2525-2530,共6页Chinese Journal of Immunology

摘　　要：目的:探讨乔松素调控TLR4/NF-κB/NLRP3信号通路对急性心肌梗死(AMI)大鼠炎症损伤的影响。方法:采用冠状动脉结扎法复制AMI模型,将大鼠分为Sham组、AMI组、Pinocembrin组(5 mg/kg尾静脉注射)、TLR4抑制剂组(TAK-242组,2.0 mg/kg尾静脉注射),检测大鼠心功能指标(LVEF、LVEDD、LVESD、FS)及血清LDH、cTnⅠ、IL-6、IL-β、TNF-α水平,TTC染色、HE染色与Masson染色观察大鼠心肌梗死及心肌组织病理学变化,TUNEL法检测心肌细胞凋亡,免疫组化及Western blot检测大鼠心肌组织TLR4/NF-κB/NLRP3通路相关蛋白。结果:与Sham组比较,AMI组大鼠心肌梗死面积增加,心肌细胞数量减少,部分心肌纤维断裂,炎症细胞浸润,胶原纤维增加,细胞凋亡率显著升高(P<0.05),LVEDD、LVESD、血清LDH、cTnⅠ、IL-6、IL-β、TNF-α水平、心肌组织TLR4、MyD88、p-NF-κB p65、NLRP3、Caspase-1表达水平显著升高(P<0.05),LVEF、FS显著降低(P<0.05);与AMI组比较,Pinocembrin组与TAK-242组大鼠心肌梗死面积减少,细胞损伤及炎症浸润减轻,坏死细胞明显减少,细胞凋亡率显著降低(P<0.05),LVEDD、LVESD、血清LDH、cTnⅠ、IL-6、IL-β、TNF-α水平、心肌组织TLR4、MyD88、p-NF-κB p65、NLRP3、Caspase-1表达水平降低(P<0.05),LVEF、FS显著升高(P<0.05);Pinocembrin组与TAK-242组大鼠各指标差异无统计学意义(P>0.05)。结论:乔松素可能通过抑制TLR4/NF-κB/NLRP3信号通路减轻AMI引起的心肌炎症损伤。Objective:To investigate the influences of Pinocembrin on inflammatory injury in rats with acute myocardial infarction(AMI)by regulating TLR4/NF-κB/NLRP3 signaling pathway.Methods:The AMI model was established by coronary ligation,and the rats were grouped into Sham group,AMI group,Pinocembrin group(5 mg/kg tail vein injection),TLR4 inhibitor group(TAK-242 group,2.0 mg/kg tail vein injection),the levels of cardiac function indexes(LVEF,LVEDD,LVESD,FS)and serum LDH,cTnⅠ,IL-6,IL-βand TNF-αwere detected in rats,TTC staining,HE staining and Masson staining were applied to observe myocardial infarction and myocardial histopathological changes in rats,cardiomyocyte apoptosis was detected by TUNEL method,immunohistochemistry and Western blot were applied to detect TLR4/NF-κB/NLRP3 pathway-related proteins in rat myocardial tissue.Results:Compared with Sham group,the myocardial infarction area increased,the number of myocardial cells decreased,some myocardial fibers were broken,inflammatory cells infiltrated,collagen fibers increased,and the apoptosis rate was obviously increased in AMI group(P<0.05),LVEDD,LVESD,serum LDH,cTnⅠ,IL-6,IL-β,TNF-αlevels,myocardial tissue TLR4,MyD88,p-NF-κB p65,NLRP3,Caspase-1 expression levels were obviously increased(P<0.05),while LVEF and FS were obviously decreased(P<0.05);compared with AMI group,the myocardial infarction area of the Pinocembrin group and the TAK-242 group were reduced,the cell damage and inflammatory infiltration were reduced,the necrotic cells were obviously reduced,and the apoptosis rate was obviously reduced(P<0.05),LVEDD,LVESD,serum LDH,cTnⅠ,IL-6,IL-β,TNF-αlevels,myocardial tissue TLR4,MyD88,p-NF-κB p65,NLRP3,Caspase-1 expression levels were decreased(P<0.05),LVEF and FS were obviously increased(P<0.05);there was no obvious difference in each index between Pinocembrin group and TAK-242 group(P>0.05).Conclusion:Pinocembrin may at-tenuate myocardial inflammatory injury caused by AMI by inhibiting TLR4/NF-κB/NLRP3 signaling pathway.

关 键 词：乔松素 急性心肌梗死 TLR4/NF-κB/NLRP3信号通路 炎症损伤 

分 类 号：R542.2[医药卫生—心血管疾病]