牛蒡子苷元对慢性心力衰竭大鼠心室重构和炎性反应的影响与机制研究  

Effect and mechanism of arctigenin on ventricular remodeling and inflammatory reaction in rats with chronic heart failure

作　　者：张婷婷 米娅莉 王维娜 左晓霞 Zhang Tingting;Mi Yali;Wang Weina;Zuo Xiaoxia(College of Nursing,Zhangjiakou University,Zhangjiakou 075000,Hebei Province,China)

机构地区：[1]张家口学院护理学院,075000 [2]张家口市第一医院心内科

出　　处：《中华老年心脑血管病杂志》2024年第3期317-321,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：河北省医学科学研究课题计划(20201592)。

摘　　要：目的 探究牛蒡子苷元(ATG)对慢性心力衰竭(CHF)大鼠心室重构和炎性反应的影响,并分析其潜在机制。方法 79只SD大鼠随机选取12只为假手术组,其余大鼠采用腹主动脉缩窄术建立CHF大鼠模型,成功造模60只大鼠随机分为CHF组、ATG低剂量组(ATG-L组,10 mg/kg)、ATG高剂量组(ATG-H组,20 mg/kg)、ATG+阴性对照(ATG+NC)组[20 mg/kg ATG+100μl高迁移率族蛋白B1(HMGB1)阴性对照质粒]、ATG+HMGB1组(20 mg/kg ATG+100μl HMGB1过表达质粒),每组12只。各组给予相应干预4周后,检测大鼠心功能、B型钠尿肽、N末端B型钠尿肽前体和炎性因子白细胞介素6、TNF-α水平、心脏质量指数和左心室质量指数、心肌组织病理变化、心肌细胞横截面积和心肌胶原体积分数、左心室心肌组织HMGB1/Toll样受体4(TLR4)/核转录因子κB(NF-κB)信号通路相关蛋白表达。结果 与假手术组比较,CHF组大鼠心肌组织HMGB1(0.42±0.05 vs 0.15±0.02)、TLR4(0.70±0.09 vs 0.21±0.04)蛋白水平和磷酸化NF-κB p65(p-NF-κB p65)/NF-κB p65(0.73±0.09 vs 0.26±0.05)蛋白比值显著升高,LVEF、左心室短轴缩短率(LVFS)显著降低(P<0.05);与CHF组比较,ATG-L组和ATG-H组大鼠心肌组织HMGB1(0.33±0.04、0.24±0.04 vs 0.42±0.05)、TLR4(0.56±0.06、0.41±0.05 vs 0.70±0.09)蛋白水平和p-NF-κB p65/NF-κB p65(0.61±0.08、0.49±0.06 vs 0.73±0.09)蛋白比值依次降低,LVEF、LVFS依次升高(P<0.05);HMGB1过表达能明显减弱ATG对HMGB1/TLR4/NF-κB信号通路和CHF大鼠心室重构、炎性反应的抑制作用(P<0.05)。结论 ATG可能通过抑制HMGB1/TLR4/NF-κB信号炎性通路,抑制了CHF大鼠的心室重构。Objective To investigate the influences of arctigenin(ATG)on ventricular remodeling and inflammatory reaction in chronic heart failure(CHF)rats,and to analyze its potential mecha-nism.Methods A total of 79SD rats were randomly divided into sham operation group(n=12),and the remaining rats were inflicted with abdominal aortic coarctation to establish a rat CHF model.After modeling,60CHF rats were randomly divided into CHF group,low and high dose ATG group(ATG-L and ATG-H groups,10and 20mg/kg,respectively),ATG+NC group[20 mg/kg ATG+100μl high mobility group protein B1(HMGB1)negative control plasmid],and ATG+HMGB1group(20mg/kg ATG+100μl HMGB1overexpression plasmid),with 12rats per group.After 4weeks of corresponding intervention,heart function,levels of B-type brain na-triuretic peptide(BNP),N-terminal B-type brain natriuretic peptide precursor(NT-proBNP)and IL-6and TNF-α,heart mass index(HMI)and left ventricular mass index(LVMI),pathological changes of myocardial tissue,cross-sectional area of myocardial cells and myocardial collagen vol-ume fraction(CVF)and protein expression of HMGB1/Toll-like receptor 4(TLR4)/NF-κB signaling pathway in left ventricular myocardial tissue were measured.Results Compared with the sham operation group,myocardial tissue HMGB1(0.42±0.05 vs 0.15±0.02)and TLR4(0.70±0.09 vs 0.21±0.04)protein levels,and phosphorylated NF-κB p65(p-NF-κB p65)/NF-κB p65(0.73±0.09 vs 0.26±0.05)protein ratio were obviously increased in the CHF group,while the left ventricular ejection fraction(LVEF)and left ventricular short-axis fractional shortening(LVFS)were obviously decreased(P<0.05).Myocardial tissue HMGB1(0.33±0.04、0.24±0.04 vs 0.42±0.05)and TLR4(0.56±0.06、0.41±0.05 vs 0.70±0.09)protein levels,and p-NF-κB p65/NF-κB p65(0.61±0.08、0.49±0.06 vs 0.73±0.09)protein ratio were decreased,and the LVEF and LVFS were increased in the ATG-L group and ATG-H group than the CHF group(P<0.05).Overexpression of HMGB1obviously attenuated the inhibitory effects of ATG on HMGB1/TLR4/NF-κB sign

关 键 词：牛蒡子苷元 心力衰竭 利钠肽 脑 肿瘤坏死因子α HMGB1/Toll样受体4/NF-κB信号通路 

分 类 号：R541.6[医药卫生—心血管疾病]