The present study was conducted to investigate the molecular mechanism of propofol in inhibiting the proliferation of mouse cardiac fibroblasts (CFs) induced by angiotensin II (Ag II). The ventricles of SPF mice from Kunming were cultured for the second to third generation of CFs under aseptic condition. On the basis of the different adding conditions, the mice were divided into five groups: (1) control group: no drug were added; (2) Ag II group: 100 nmol/L Ag II were added; (3) 10 μmol/L propofol + 100 nmol/L Ag II group; (4) 30 μmol/L propofol + 100 nmol/L Ag II group; (5) 50 μmol/L propofol + 100 nmol/L Ag II group. The effects of propofol on the proliferation of CFs induced by Ag II, the expression of CFs ET-1, the activity of NADPH oxidase and the formation of ROS were analyzed. In addition, our study also explored the potential role of Akt-eNOS-nitric oxide pathway regarding the inhibition of proliferation of Ag II induced CFs by propofol. We found that the proliferation of CFs, the secretion of ET-1, the activity of NADPH oxidase and the level of intracellular ROS and fibronectin expression were significantly increased after CFs exposure to Ag II for 24 h. The abovementioned indexes decreased significantly in CFs after treated with propofol for 24 h (10, 30, or 50 μmol/L) with significant statistical difference (P < 0.05). Akt and eNOS siRNA transfection significantly decreased the levels of Akt and eNOS protein, respectively. Blocking pathway of Akt-eNOS-nitric oxide decreased the inhibitory effect of propofol on Ag II-induced cell proliferation of CFs. Propofol exerts effect in inhibiting ET-1 and fibronectin expression and the formation of ROS induced by Ag II. Moreover, Akt-eNOS-nitric oxide signaling pathway may be involved in the effect of propofol on the proliferation of CFs induced by Ag II.

中文翻译：

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丙泊酚在血管紧张素II诱导的小鼠中抑制心肌成纤维细胞增殖的评估。

本研究旨在研究异丙酚抑制血管紧张素II（Ag II）诱导的小鼠心脏成纤维细胞（CFs）增殖的分子机制。将昆明的SPF小鼠的心室在无菌条件下培养第二代至第三代CF。根据不同的添加条件，将小鼠分为五组：（1）对照组：不添加药物；（2）Ag II组：加入100nmol / L的Ag II；（3）10μmol/ L异丙酚+ 100 nmol / L Ag II组; （4）30μmol/ L异丙酚+ 100 nmol / L Ag II组; （5）50μmol/ L异丙酚+ 100 nmol / L Ag II组。分析了异丙酚对Ag II诱导的CFs增殖，CFs ET-1表达，NADPH氧化酶活性和ROS形成的影响。此外，我们的研究还探讨了Akt-eNOS-一氧化氮途径在异丙酚抑制Ag II诱导的CFs增殖中的潜在作用。我们发现CFs暴露于Ag II 24 h后，CFs的增殖，ET-1的分泌，NADPH氧化酶的活性以及细胞内ROS和纤连蛋白的表达均显着增加。异丙酚处理24 h（10、30或50μmol/ L）后，CFs的上述指标显着降低，差异有统计学意义（P <0.05）。Akt和eNOS siRNA转染分别显着降低了Akt和eNOS蛋白的水平。Akt-eNOS-一氧化氮的阻断途径降低了异丙酚对Ag II诱导的CFs细胞增殖的抑制作用。丙泊酚在抑制ET-1和纤连蛋白的表达以及Ag II诱导的ROS的形成方面发挥作用。此外，Akt-eNOS-一氧化氮信号通路可能参与了异丙酚对Ag II诱导的CFs增殖的影响。