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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
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| 篇名： | 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 |
| TITLE： | Effects of leonurine on myocardial injury in rats with coronary heart disease by regulating the GAS6/Axl signaling pathway |
| 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、100mg/kg益母草碱+腹腔注射75mg/kg生理盐水），益母草碱高剂量+GAS6/Axl信号通路抑制剂组（灌胃100mg/kg益母草碱+腹腔注射75mg/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48d。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。 |
| ABSTRACT： | 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 R428 75 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. |
| 期刊： | 2025年第36卷第01期 |
| 作者： | 孟王桃；崔冬玲；吴冬景；陈超；张颖颖 |
| AUTHORS： | MENG Wangtao，CUI Dongling，WU Dongjing，CHEN Chao，ZHANG Yingying |
| 关键字： | 益母草碱；GAS6/Axl信号通路；冠心病；心肌损伤 |
| KEYWORDS： | leonurine； GAS6/Axl signaling pathway； |
| 阅读数： | 5 次 |
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