Study on Mechanism of Nuanxinkang(暖心康)on Improving Cardiac Function in Mice with Ischemic Heart Failure Based on Neutrophil Extracellular Traps
Objective To investigate the mechanism of Nuanxinkang(暖心康)on improving ventricular remodeling and cardi-ac function in mice with ischemic heart failure by interfering with the formation of neutrophil extracellular traps,therefore inhibi-ting inflammation,maintaining the homeostasis of cardiomyocytes and preventing cardiomyocytes from damage.Methods Thirty a-dult 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 factorα(TNF-α)and expres-sion 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 periph-eral 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 in-creased,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 expres-sion of MPO in heart tissue increased and the mRNA expression level of it became significantly higher(P＜0.001).The content of CitH3 in peripheral blood increased(P＜0.001).Compared with those of the model group,in the Nunxinkang group,the am-plitude of ventricular wall motion increased,the values of LVEF and LVFS decreased(P＜0.05).The infiltration of inflammatory cells in heart tissue was reduced and the structure and arrangement of myocardial cells were improved.The mRNA expressions of BNP,IL-6,IL-1β and TNF-α decreased(P＜0.05).The protein expression of MPO decreased significantly and the mRNA expression level showed the same trend(P＜0.001).The content of CitH3 in peripheral blood decreased(P＜0.001).Conclu-sion Nuanxinkang can improve the cardiac function of mice with ischemic heart failure,and its mechanism may be achieved by in-terfering with the formation of neutrophil extracellular traps,therefore inhibiting inflammatory reaction,improving the homeostasis of cardiomyocytes,reducing myocardial cell damage and eventually improving the ventricular remodeling of mice with ischemic heart failure.
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