目的 通过体内外实验，探讨人参糖蛋白对阿霉素心脏毒性的保护作用及机制。方法 建立SD大鼠心肌损伤模型，给予人参糖蛋白进行干预后，检测血清中乳酸脱氢酶（lactate dehydrogenase，LDH）、肌酸激酶同工酶MB（creatine kinase isoenzymes-MB，CK-MB）、超氧化物歧化酶（superoxide dismutase，SOD）活性及谷胱甘肽（glutathione，GSH）水平；采用苏木素-伊红（HE）染色法观察大鼠心肌组织病理变化。建立心肌细胞H9c2损伤模型，采用CCK-8法检测H9c2细胞活力；通过流式细胞术检测H9c2细胞周期、细胞凋亡、活性氧（reactive oxygen species，ROS）水平和线粒体膜电位变化；采用Western blotting法检测H9c2细胞凋亡相关蛋白、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路相关蛋白、沉默信息调节因子2相关酶类3（silent mating type information regulation 2 homolog 3，Sirt3）的表达情况。结果 心肌损伤大鼠模型中，模型组大鼠心肌纤维排列紊乱，肌纤维严重变性，LDH和CK-MB活性显著升高（P<0.01），SOD活性和GSH水平显著降低（P<0.05、0.01）；与模型组比较，人参糖蛋白高剂量组心肌肌束排列较为整齐，LDH和CK-MB活性显著下降（P<0.05），GSH水平显著升高（P<0.05），人参糖蛋白对阿霉素所致的心肌组织病理学损伤有明显修复作用。细胞损伤模型中，模型组细胞存活率显著下降（P<0.001），细胞周期阻滞于G₁期（P<0.01），细胞凋亡显著升高（P<0.01），ROS水平显著升高（P<0.01），线粒体膜电位显著下降（P<0.01），Sirt3、Caspase-3、B淋巴细胞瘤-2（B cell lymphoma-2，Bcl-2）蛋白表达水平显著降低（P<0.01），Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）、细胞色素C（cytochrome C，Cyt C）、c-Jun氨基末端激酶（c-Jun N-terminal kinase，JNK）、p38、细胞外调节蛋白激酶1/2（extracellular regulated protein kinases 1/2，ERK1/2）蛋白表达水平显著升高（P<0.05、0.01）；与模型组比较，人参糖蛋白组细胞存活率显著升高（P<0.05、0.01），细胞增殖周期恢复，细胞凋亡率显著降低（P<0.05），ROS水平显著降低（P<0.05），线粒体膜电位显著升高（P<0.05），Sirt3、Caspase-3、Bcl-2蛋白表达水平显著升高（P<0.05），Bax、Cyt C、JNK、p38、ERK1/2蛋白表达水平显著降低（P<0.05）。结论 人参糖蛋白能够通过抗氧化应激、降低线粒体膜电位、提高H9c2细胞内ROS水平并调控MAPK信号通路抑制细胞凋亡，从而保护阿霉素诱导的心肌损伤。

Objective In vitro and in vivo experiments were conducted to investigate the protective effect and mechanism of ginseng glycoproteins on adriamycin-induced cardiotoxicity. Methods SD rats myocardial injury model was established. After intervention with ginseng glycoprotein, activities of lactate dehydrogenase (LDH), creatine kinase isoenzymes-MB ​​(CK-MB), and superoxide dismutase (SOD) and glutathione (GSH) levels in serum were detected; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of rat myocardial tissue. H9c2 injury model of cardiomyocytes was established, and viability of H9c2 cells was detected by CCK-8 method; H9c2 cells cycle, apoptosis, reactive oxygen species (ROS) levels and mitochondrial membrane potential changes in mitochondrial membrane potential were detected by flow cytometry; Western blotting was used to detect expressions of apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway related proteins and silent information regulator 2 related enzymes 3 (Sirt3) in H9c2 cells. Results In myocardial injury rats model, the myocardial fiber arrangement of model group was disordered, the muscle fiber was severely degenerated, the activities of LDH and CK-MB were significantly increased (P < 0.01), and the SOD activity and GSH level were significantly decreased (P < 0.05, 0.01); Compared with model group, the myocardial muscle bundles in high-dose ginseng glycoprotein group were arranged more neatly, activities of LDH and CK-MB were significantly decreased (P < 0.05), and level of GSH was significantly increased (P < 0.05). The pathological damage of myocardial tissue caused by adriamycin had obvious repairing effect. In cell injury model, cell viability of model group was significantly decreased (P < 0.001), cell cycle was arrested in G₁ phase (P < 0.01), apoptosis was significantly increased (P < 0.01), and level of ROS was significantly increased (P < 0.01), mitochondrial membrane potential was significantly decreased (P < 0.01), expressions of Sirt3, Caspase-3, B cell lymphoma-2 (Bcl-2) were significantly decreased (P < 0.01), expressions of Bcl-2 associated X protein (Bax), cytochrome C (Cyt C), c-Jun N-terminal kinase (JNK), p38, extracellular regulated protein kinases 1/2 (ERK1/2) were significantly increased (P < 0.05, 0.01); Compared with model group, cell viability of ginseng glycoprotein group was significantly increased (P < 0.05, 0.01), cell proliferation cycle was restored, and apoptosis rate was significantly reduced (P < 0.05), ROS level was significantly reduced (P < 0.05), and mitochondrial membrane potential was significantly increased (P < 0.05), expressions of Sirt3, Caspase-3 and Bcl-2 in ginseng glycoprotein group were significantly increased (P < 0.05), expressions of Bax, Cyt C, JNK, p38, ERK1/2 were significantly reduced (P < 0.05). Conclusion Ginseng glycoprotein can prevent oxidative stress, reduce mitochondrial membrane potential, increase ROS level in H9c2 cells, and regulate MAPK signaling pathway to inhibit cell apoptosis, thereby protecting adriamycin-induced myocardial injury.

R285.5

国家自然科学基金资助项目（81803680）；吉林省科技发展项目（20170309005YY）；吉林省中医药科技项目（2020041）