益母草碱调节GAS6/Axl信号通路对冠心病大鼠心肌损伤的影响  

Effects of leonurine on myocardial injury in rats with coronary heart disease by regulating the GAS6/Axl signaling pathway

作　　者：孟王桃 崔冬玲 吴冬景 陈超[1] 张颖颖[1] MENG Wangtao;CUI Dongling;WU Dongjing;CHEN Chao;ZHANG Yingying(School of Nursing,Xinyang Vocational and Technical College,Henan Xinyang 464000,China)

机构地区：[1]信阳职业技术学院护理学院,河南信阳464000

出　　处：《中国药房》2025年第1期51-56,共6页China Pharmacy

基　　金：河南省高等学校重点科研项目计划(No.23B320017)。

摘　　要：目的探讨益母草碱对生长停滞特异性蛋白6(GAS6)/酪氨酸蛋白激酶受体(Axl)信号通路的影响,阐明其减轻冠心病大鼠心肌损伤的机制。方法构建冠心病大鼠模型,将造模成功的大鼠按随机抽样方法分为模型组,益母草碱低、高剂量组(分别灌胃25、100 mg/kg益母草碱+腹腔注射75 mg/kg生理盐水),益母草碱高剂量+GAS6/Axl信号通路抑制剂组(灌胃100 mg/kg益母草碱+腹腔注射75 mg/kg的R428),每组12只;另取12只正常大鼠作对照组。各给药组大鼠给予相应药物,对照组和模型组大鼠灌胃并腹腔注射等体积生理盐水,每天1次,连续48 d。给药结束后,检测大鼠心功能和血清中炎症因子及心肌损伤标志物水平;观察其心肌组织病理形态;检测其心肌组织细胞凋亡率和心肌组织中凋亡及GAS6/Axl信号通路相关蛋白表达。结果与对照组比较,模型组大鼠出现心肌细胞与心肌纤维排列紊乱、心肌细胞肥大、细胞核固缩等病变,左室射血分数、左室短轴缩短率、二尖瓣环舒张早期与舒张晚期运动速度之比及GAS6蛋白相对表达量和B细胞淋巴瘤2/B细胞淋巴瘤2相关X蛋白、磷酸化Axl/Axl比值均显著降低(P<0.05),肿瘤坏死因子α、白细胞介素1β、白细胞介素6、肌酸激酶同工酶、肌钙蛋白Ⅰ、肌红蛋白水平以及心肌组织细胞凋亡率和剪切型胱天蛋白酶3/胱天蛋白酶3比值均显著升高(P<0.05);益母草碱各剂量组大鼠上述病理情况及各检测指标均显著改善(P<0.05),且益母草碱高剂量组效果较益母草碱低剂量组明显(P<0.05);R428处理可逆转高剂量益母草碱对冠心病大鼠心肌损伤的改善作用(P<0.05)。结论益母草碱可减轻冠心病大鼠心肌损伤,其作用机制可能与激活GAS6/Axl信号通路相关。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 lowdose 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,troponinⅠand 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 detectio

关 键 词：益母草碱 GAS6/Axl信号通路 冠心病 心肌损伤 

分 类 号：R965[医药卫生—药理学] R541.4[医药卫生—药学]