基于IKK/IκB/NF-κB信号通路探讨养心颗粒干预急性心肌梗死后心室重构的作用机制  

Based on IKK/IκB/NF-κB Signaling Pathway to Explore the Mechanism of Yangxin Granule in the Intervention of Ventricular Remodeling after Acute Myocardial Infarction

作　　者：姜芊竹[1] 张琪[2] 杨建飞[2] 万冬梅[1] 孙静[2] 邢露茗 封笑 周亚滨[2] JIANG Qianzhu;ZHANG Qi;YANG Jianfei;WAN Dongmei;SUN Jing;XING Luming;FENG Xiao;ZHOU Yabin(Second Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150001,Heilongjiang,China)

机构地区：[1]黑龙江中医药大学附属第二医院,哈尔滨150001 [2]黑龙江中医药大学附属第一医院,哈尔滨150040

出　　处：《中西医结合心脑血管病杂志》2022年第3期427-431,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：黑龙江省中医药科研项目(No.ZHY2020-158)。

摘　　要：目的探讨养心颗粒对抗大鼠急性心肌梗死后心室重构的作用,并通过IKK/IκB/NF-κB信号通路探讨其作用机制。方法将60只SD大鼠,按照体质量随机分为假手术组(12只)和手术组(48只),手术组大鼠结扎冠状动脉左前降支,复制急性心肌缺血模型。假手术组只穿线,不结扎。将模型复制成功的36只大鼠随机分为模型组、养心颗粒组、依那普利组,每组12只。养心颗粒组大鼠每日灌胃养心颗粒12.07 g/kg;依那普利组每日灌胃依那普利混悬液10 mg/kg;模型组和假手术组灌胃等体积的生理盐水。连续给药8周后,取静脉血,酶联免疫吸附法(ELISA)测定其中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)水平;取梗死部位心肌组织,苏木精-伊红(HE)染色后电镜下观察大鼠心肌组织病理学变化,ELISA测定梗死心肌组织肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、干扰素-γ(IFN-γ)含量;蛋白免疫印迹法(Western Blot)测定心肌组织核转录因子-κB(NF-κB)p65、抑制性核因子激酶κB-β(IKK-β)、核转录因子κB抑制剂(IκB-α)和磷酸化的IκB-α(p-IκBα)蛋白的表达。结果与模型组比较,养心颗粒组大鼠心肌细胞肿胀和变形有所减轻,胶原纤维增生和炎性细胞浸润减少,外周血MMP-2浓度、心肌组织TNF-α、IL-1β、IL-6、IFN-γ水平及NF-κBp65和p-IκB蛋白的表达均明显降低(P<0.05),外周血TIMP-2浓度、心肌组织IKK-β和IκB-α蛋白的表达则明显升高(P<0.05)。养心颗粒组与依那普利组大鼠的以上指标比较,差异均无统计学意义(P>0.05)。结论养心颗粒可以缓解急性心肌梗死后大鼠的心室重构,其作用机制与降低炎性细胞因子水平、调控IKK/IκB/NF-κB信号通路密切相关,且作用效果与依那普利相当。Objective To investigate the effect of Yangxin Granule on ventricular remodeling after acute myocardial infarction in rats,and to explore its mechanism through IKK/IκB/NF-κB signaling pathway.Methods Sixty Sprague-Dawley(SD)rats were randomly divided into sham operation group(n=12)and operation group(n=48)according to body weight.Rats in the operation group,the left anterior descending coronary artery was lighted to create acute myocardial ischemia(AMI)model.In the sham operation group,threading was performed,without ligation of coronary artery.Thirty-six rats which AMI model were successfully duplicated were randomly divided into model group,Yangxin Granule group,and enalapril group,with 12 rats in each group.Rats in Yangxin Granule group were given 12.07 g/kg of Yangxin Granule every day.Enalapril group was given 10 mg/kg enalapril suspension by gavage daily.Model group and sham operation group were given intragastrically with equal volume of normal saline.After 8 weeks of continuous administration,the levels of matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-2(TIMP-2)in venous blood were determined by enzyme-linked immunosorbent assay(ELISA).The histopathological changes of myocardial tissue were observed under electron microscope after hematoxylin-eosin(HE)staining.The contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interferon-γ(IFN-γ)in myocardial tissue were determined by ELISA.The expression of nuclear factor-κB(NF-κB)P65,inhibitory nuclear factor kinaseκB-β(IKK-β),nuclear factorκB inhibitor(IκB-α)and phosphorylated protein IκB-α(P-IκBα)were determined by Western Blot.Results Compared with model group,the swelling and deformation of myocardial cells in Yangxin Granule group were reduced,collagen fiber hyperplasia and inflammatory infiltration were reduced,MMP-2 concentration in peripheral blood,TNF-α,IL-1β,IL-6,and IFN-γlevels in myocardial tissue and the expression of NF-κBp65,and p-IκB protein were decreased sign

关 键 词：急性心肌缺血 心室重构 养心颗粒 IKK/IκB/NF-κB信号通路 实验研究 

分 类 号：R54[医药卫生—心血管疾病]