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As the end stage of various cardiovascular diseases, heart failure is still a disease with high mortality and complicated pathophysiological mechanisms. Over-activation of sympathetic system was considered as one of the common characters of heart failure. Qishen Granule (QSG), a Chinese Medicine formula, showed great effect on heart failure induced by left coronary artery ligation in rat, which was composed of Huangqi (Astragalus membranaceus), Danshen (Salvia miltiorrhiza), etc. In this study, we will investigate on the effect of QSG on heart failure induced by over-activation of sympathetic system, and explore its potential mechanism by network pharmacological analysis.
Healthy male C57BL/6 mice (20g±1g) were divided into 4 groups randomly, including a model group, a QSG group, a Fosinopril group and a control group. Except the control group, heart failure was induced by subcutaneous injection of gradient isoproterenol (ISO) (20mg/kg for the first day; 10mg/kg for the second day; 5mg/kg per day from the third day to the fourteenth day). At the same time, QSG (44mg/kg/d) or Fosinopril (5.5mg/kg/d) were given by gavage administration according to the group from the first day. After 14 days treatment, heart index was calculated by heart weight/ body weight, heart function was detected by echocardiography, and pathological changes were evaluated by Hematoxylin-Eosin staining of cardiac tissue. And then the potential targets of QSG were analyzed by bioinformatics analysis tool (BATMAN-TCM).
Comparing with model group, left ventricular internal systolic diameter( QSG vs. model, 2.68±0.47 vs. 3.52±0.52, mm, P<0.05) and heart index (QSG vs. model, 4.95±0.13 vs. 3.52±0.52, mg/g, P<0.05) were significantly reduced in QSG group, while the ejection fraction (QSG vs. model, 57.3±7.20 vs. 44.2±10.51, %, P<0.05) and fractional shortening (QSG vs. model, 30.43±4.12 vs. 22.01±6.01, %, P<0.05) were dramatically improved. Hematoxylin-Eosin staining showed that the pathological lesions were decreased in QSG group, such as the hypertrophy of the cardiomyocytes and thickening of vascular wall. Similar changes were found in Fosinopril treated animals. Network pharmacological predication showed that multiple targets were related to the effect of QSG, including adrenoceptor alpha 2A (ADRA2A), adrenoceptor alpha 2B (ADRA2B), angiotensin converting enzyme (ACE), etc.
QSG significantly improved the heart function of heart failure induced by overdose isoproterenol in mice. These effects may be related to the regulation of sympathetic nervous system and catecholamine system, reduction of Angiotensin II and inhibition of Renin angiotensin system (RAS) activity, etc. The precise targets and mechanism of QSG still need more experiments to verify.