You Wei, Wu Zhiming, Ye Fei, Wu Xiangqi
Pharmazie. 2018 Sep 1;73(9):508-512. doi: 10.1691/ph.2018.8600.
The mTORC1-dependent signaling pathway is mainly involved in the adverse left ventricular remodeling (ALVR) process after myocardial infarction (MI). However, whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not reported. Twenty mice were randomly assigned into three groups: sham group (10 ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin-treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an intraperitoneal injection accordingly for two weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes and cell apoptosis of border area were evaluated using Masson's staining, WGA staining and TUNEL assay, respectively. The 4E-binding protein 1 (4E-BP1) and ribosomal S6 (S6) in myocardium were determined by western blot. mTOR-Raptor association was tested by co-immunoprecipitation assay in H9C2 cell line. Treatment with cardamonin, MI mice displayed that heart hypertrophy and heart dysfunction were alleviated, and cardiac fibrosis, cardiomyocyte size and cell apoptosis of border area were decreased (P<0.05). Besides, cardamonin can inhibit 4E-BP1 and S6 phosphorylation in heart of MI mice and H9C2 cell line (P<0.05). Furthermore, cardamonin disrupted mTOR-Raptor association in vitro. Cardamonin exerted cardio-protection against ALVR through mTORC1 inhibition.
哺乳动物雷帕霉素靶蛋白复合体1（mTORC1）依赖性信号通路主要参与心肌梗死后的不良左心室重构（ALVR）过程。然而，小豆蔻明抑制mTORC1是否能减轻心肌梗死后的ALVR仍未见报道。将20只小鼠随机分为三组：假手术组（10 ml/kg/天磷酸盐缓冲液，n = 6）、模型组（心肌梗死+10 ml/kg/天磷酸盐缓冲液，n = 7）和小豆蔻明治疗组（心肌梗死+20 mg/kg/天小豆蔻明，n = 7）。所有组均相应地腹腔注射两周。测量心脏和体重。通过超声心动图评估心脏功能。分别使用Masson染色、小麦胚凝集素（WGA）染色和TUNEL检测评估梗死周边区的胶原沉积、心肌细胞面积和细胞凋亡。通过蛋白质免疫印迹法测定心肌中的4E结合蛋白1（4E-BP1）和核糖体S6（S6）。在H9C2细胞系中通过免疫共沉淀试验检测mTOR-雷帕霉素靶蛋白（Raptor）的相互作用。小豆蔻明治疗的心肌梗死小鼠显示，心脏肥大和心脏功能障碍得到缓解，梗死周边区的心脏纤维化、心肌细胞大小和细胞凋亡减少（P<0.05）。此外，小豆蔻明可抑制心肌梗死小鼠心脏和H9C2细胞系中4E-BP1和S6的磷酸化（P<0.05）。此外，小豆蔻明在体外破坏了mTOR-Raptor的相互作用。小豆蔻明通过抑制mTORC1对ALVR发挥心脏保护作用。
