摘要
目的探讨暖心康通过干预中性粒细胞胞外诱捕网形成,抑制炎症反应,改善心肌细胞内环境稳态,减少心肌细胞损伤,从而改善缺血性心衰小鼠心室重塑,提高心功能的作用机制。方法将30只成年健康雄性C57BL/6J小鼠随机分为3组:假手术组、模型组、暖心康组,模型组与暖心康组结扎冠状动脉左前降支建立缺血性心衰小鼠模型,假手术组仅开胸但不结扎冠状动脉。暖心康组给予暖心康灌胃,假手术组和模型组给予等量0.9%氯化钠溶液灌胃,1次/d,持续4周。对每组小鼠行心脏彩超检测左室射血分数(left ventricular ejection fraction,LVEF)、左室缩短分数(left ventricular fractional shortening,LVFS);苏木精-伊红染色法(Hematoxylin-eosin staining,HE)染色、天狼星红染色检测心肌结构及纤维化程度,RT-PCR检测各组心肌组织脑钠肽(Brain Natriuretic Peptide,BNP)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-1β(Interleukin-1β,IL-1β)、肿瘤坏死因子α(Tumor Necrosis Factor-alpha,TNF-α)、髓过氧化物酶(myeloperoxidase,MPO)的表达;免疫组化染色(immunohistochemistry,IHC)观察MPO在心脏中的表达情况,酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测小鼠外周血瓜氨酸化组蛋白3(citrullinated histone 3,CitH3)水平。结果与假手术组比较,模型组小鼠室壁运动幅度减弱,LVEF、LVFS显著降低(P<0.01),心脏组织炎性细胞浸润增多,心肌细胞肥大、排列紊乱,胶原纤维增多,心衰标志物BNP与炎症因子IL-6、IL-1β、TNF-α的mRNA表达水平升高(P<0.01),心脏组织中MPO的蛋白表达明显增多,mRNA表达水平显著升高(P<0.001),外周血CitH3含量显著升高(P<0.001);与模型组比较,暖心康组小鼠室壁运动幅度增大,左室射血分数、左室缩短分数升高(P<0.05),心脏组织炎性细胞浸润减少,心肌细胞结构与排列改善,心衰标志物BNP与炎症因子IL-6、IL-1β、TNF-α的mRNA表达水平降低(P<0.05),MPO�
Objective To investigate the mechanism of Nuanxinkang(暖心康)on improving ventricular remodeling and cardiac function in mice with ischemic heart failure by interfering with the formation of neutrophil extracellular traps,therefore inhibiting inflammation,maintaining the homeostasis of cardiomyocytes and preventing cardiomyocytes from damage.Methods Thirty adult healthy male C57BL/6J mice were randomly divided into three groups:sham operation group,model group and Nuanxinkang group.The model of ischemic heart failure which performed by model group and Nuanxinkang group was established by ligating the left anterior descending branch of the coronary artery.The sham operation group only opened the chest but did not ligate the coronary artery.Nuanxinkang group was given Nuanxinkang by gavage while sham operation group and model group were given 0.9%sodium chloride solution by gavage once a day for 4 weeks.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were detected by color Doppler echocardiography in each group of mice.Hematoxylin eosin staining(HE)and Sirius red staining were used to detect myocardial structure and fibrosis degree,and RT-PCR was used to detect brain natriuretic peptide(BNP),interleukin-6(IL-6)and interleukin-1(IL-1β),tumor necrosis factor α(TNF-α)and expression of myeloperoxidase(MPO).Immunohistochemistry(IHC)method was used to observe the expression of MPO in the heart and enzyme-linked immunosorbent assay(ELASA)was used to detect the level of citrullinated histone 3(CitH3)in the peripheral blood of mice.Results Compared with those of the sham operation group,in the model group,the amplitude of ventricular wall motion decreased,the values of LVEF and LVFS were decreased(P<0.01).Inflammatory cell infiltration in heart tissue increased,cardiomyocytes became hypertrophy and disordered,and collagen fibers increased.The mRNA expression level of heart failure marker BNP and inflammatory factors IL-6,IL-1β and TNF-α increased(P<0.01).Meanwhile,the protein
作者
李玄
林祉均
陈梓欣
董鑫
江佳林
关卓骥
黎欢
李志芳
王陵军
陈洁
冼绍祥
LI Xuan;LIN Zhijun;CHEN Zixin;DONG Xin;JIANG Jialin;GUAN Zhuoji;LI Huan;LI Zhifang;WANG Lingjun;CHEN Jie;XIAN Shaoxiang(Guangzhou University of Chinese Medicine,Guangzhou 510405,Guandong,China;Lingnan Medical Research Center of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guandong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guandong,China;Shenzhen hospital of Integrated Chinese and Western Medicine,Shenzhen 518104,Guangdong,China)
出处
《中华中医药学刊》
CAS
北大核心
2024年第2期175-178,I0027-I0029,共7页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81973777,82004293)
广东省中医药局科研项目(20211145)
深圳市医疗卫生三名工程项目(SZZYSM202106006)
广州市科技计划项目(202201020342)。
关键词
中性粒细胞胞外诱捕网
炎症因子
缺血性心力衰竭
暖心康
neutrophil extracellular traps
inflammatory factor
ischemic heart failure
Nuanxinkang(暖心康)
