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汉黄芩素调节NF-κB/MAPK信号通路对心肌缺血再灌注损伤大鼠炎症损伤的影响

Impact of wogonin on inflammatory injury in rats with myocardial ischemia-reperfusion injury by regulating NF-κB/MAPK signaling pathway
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摘要 目的:探讨汉黄芩素对心肌缺血再灌注(MI/R)损伤大鼠的保护作用,并分析其潜在机制。方法:SD大鼠随机分为假手术组、MI/R组、曲美他嗪组(10 mg/kg)、汉黄芩素低、中、高剂量组(5、10、20 mg/kg),每组12只。采用结扎左前降支冠状动脉30 min,再灌注24 h建立MI/R模型。超声心动图检测大鼠心功能,ELISA检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性和TNF-α、IL-6、IL-1β水平;TTC染色检测心肌梗死面积;HE染色检测心肌组织病理学变化;TUNEL染色检测心肌细胞凋亡水平;免疫组织化学(IHC)检测心肌组织核因子-κB(NF-κB) p65表达;Western blot检测心肌组织凋亡和NF-κB/丝裂原活化蛋白激酶(MAPK)通路相关蛋白表达。结果:与假手术组相比,MI/R组大鼠LVESD、LVEDD、血清CK-MB、LDH活性和IL-6、IL-1β和TNF-α水平、心肌梗死面积百分比、心肌细胞凋亡率、Bax蛋白水平、核NF-κB p65表达以及Cleaved-Caspase-3/Caspase-3、p-P38 MAPK/P38 MAPK显著升高,EF、FS、Bcl-2蛋白水平显著降低(P<0.05),心肌纤维排列紊乱,大量炎症细胞浸润;与MI/R组相比,曲美他嗪组和汉黄芩素高、中、低剂量组大鼠LVESD、LVEDD、血清CK-MB、LDH活性和IL-6、IL-1β和TNF-α水平、心肌梗死面积百分比、心肌细胞凋亡率、Bax蛋白水平、核NF-κB p65表达以及Cleaved-Caspase-3/Caspase-3、p-P38 MAPK/P38 MAPK显著降低,EF、FS、Bcl-2蛋白水平显著升高(P<0.05),心肌炎症细胞浸润和肌纤维断裂减少,且呈剂量依赖性。结论:汉黄芩素可能通过抑制NF-κB/MAPK信号通路抑制炎症反应和心肌细胞凋亡,改善大鼠MI/R损伤。 Objective:To investigate protective effect of wogonin on myocardial ischemia/reperfusion(MI/R)injury in rats,and to analyze its potential mechanism.Methods:SD rats were randomly separated into sham operation group,MI/R group,trimetazi-dine group(10 mg/kg),wogonin low,medium and high doses groups(5,10,20 mg/kg),with 12 rars per group.MI/R model was established by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h.Echocardiography was applied to detect cardiac function in rats,ELISA was applied to detect activities of serum lactate dehydrogenase(LDH),creatine kinase isoen-zyme(CK-MB)and levels of TNF-α,IL-6 and IL-1βin rats;TTC staining was applied to detect myocardial infarct size;HE staining was applied to detect myocardial histopathological changes;TUNEL staining was applied to detect apoptosis level of cardiomyocytes;immunohistochemistry(IHC)method was applied to detect expression of nuclear factor-κB(NF-κB)p65 in myocardial tissue;Western blot was applied to detect myocardial apoptosis and expressions of NF-κB/mitogen-activated protein kinase(MAPK)pathway-related proteins.Results:Compared with sham operation group,LVESD,LVEDD,serum CK-MB and LDH activities,levels of IL-6,IL-1βand TNF-α,myocardial infarction area percentage,myocardial cell apoptosis rate,protein level of Bax,expression of nuclear NF-κB p65,and Cleaved-Caspase-3/Caspase-3,p-P38 MAPK/P38 MAPK in MI/R group were obviously increased,EF,FS and pro-tein levels of Bcl-2 were obviously decreased(P<0.05),myocardial fibers were disordered,and a large number of inflammatory cells were infiltrated;compared with MI/R group,LVESD,LVEDD,serum CK-MB and LDH activities,levels of IL-6,IL-1βand TNF-α,myocardial infarction area percentage,myocardial cell apoptosis rate,protein level of Bax,expression of nuclear NF-κB p65,and Cleaved-Caspase-3/Caspase-3 and p-P38 MAPK/P38 MAPK in trimetazidine group and wogonin high,medium and low doses groups were obviously decreased,EF,FS and protein levels of Bcl-2 were obviously increased(P<0.05),myocardial inflammatory cell infil-tration and muscle fiber fragmentation were reduced in a dose-dependent manner.Conclusion:Wogonin may improve MI/R injury in rats by inhibiting NF-κB/MAPK signaling pathway,inhibiting inflammatory response and cardiomyocyte apoptosis.
作者 王蕾 李强 姚书霞 WANG Lei;LI Qiang;YAO Shuxia(The Fourth Department of Cardiology,the First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China)
出处 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第11期2335-2342,共8页 Chinese Journal of Immunology
关键词 汉黄芩素 心肌缺血再灌注 炎症反应 核因子-ΚB 丝裂原活化蛋白激酶 Wogonin Myocardial ischemia/reperfusion Inflammatory response NF-κB Mitogen-activated protein kinase
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