1.Effects of leonurine on myocardial injury in rats with coronary heart disease by regulating the GAS6/Axl signaling pathway
Wangtao MENG ; Dongling CUI ; Dongjing WU ; Chao CHEN ; Yingying ZHANG
China Pharmacy 2025;36(1):51-56
OBJECTIVE To explore the effects of leonurine on growth arrest-specific protein-6 (GAS6)/Axl signaling pathway,and clarify its mechanism of alleviating myocardial injury in rats with coronary heart disease.METHODS The rat model of coronary heart disease was constructed;successfully modeled rats were randomly separated into model group,leonurine low-dose and high-dose groups (intragastric administration of leonurine 25,100 mg/kg+intraperitoneal injection of normal saline 75 mg/kg),and leonurine high-dose+GAS6/Axl signaling pathway inhibitor group (intragastric administration of leonurine 100 mg/kg+intraperitoneal injection of R42875 mg/kg),with 12 rats in each group.Additional 12 normal rats were selected as control group.Each administration group was given relevant medicine;control group and model group were given a constant volume of normal saline intragastrically and intraperitoneally,once a day,for 48 consecutive days.After administration,the heart function of rats,and serum levels of inflammatory factors and myocardial injury markers were detected;the pathological morphology of myocardial tissue was observed;the myocardial cell apoptosis rate,the expressions of apoptosis and GAS6/Axl signaling pathway-related proteins were determined.RESULTS Compared with control group,model group showed disorders in the arrangement of myocardial cells and myocardial fibers,hypertrophy of myocardial cells,and nuclear condensation;left ventricular ejection fraction,left ventricular fractional shortening,ratio of early-diastolic and late-diastolic motion velocity of the mitral ring,the protein expression of GAS6,B-cell lymphoma 2/B-cell lymphoma 2 associated X protein and phosphorylated Axl/Axl ratios were decreased significantly (P<0.05).The levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,creatine kinase isoenzyme,troponin Ⅰ and myoglobin,the cell apoptosis rate,and cleaved caspase-3/caspase-3 ratio were increased significantly (P<0.05).Leonurine could obviously improve the above pathological conditions and detection indicators (P<0.05),and the effect of leonurine high-dose group was more significant than that of leonurine low-dose group (P<0.05);R428 treatment could reverse the ameliorating effect of high-dose of leonurine on myocardial injury in rats with coronary heart disease (P<0.05).CONCLUSIONS Leonurine can alleviate myocardial injury in rats with coronary heart disease,and its mechanism of action is related to the activation of the GAS6/Axl signaling pathway.

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