Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New District, Shanghai 201203, China.
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Shanghai 200032, China.
Cardiovasc Ther. 2020 Apr 29;2020:8584763. doi: 10.1155/2020/8584763. eCollection 2020.
Although many studies have been performed to elucidate the molecular mechanisms of heart failure, an effective pharmacological therapy to protect cardiac tissues from severe loss of contractile function associated with heart failure after acute myocardial infarction (MI) has yet to be developed.
We examined the cardioprotective effects of ()-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid, a new compound with potent antioxidant and antiapoptotic activities in a rat model of heart failure. ()-2-Acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid was systemically delivered to rats 6 weeks after MI at different doses (15, 30, and 60 mg/kg). Cardiac function was assessed by hemodynamic measurements. The expression of proinflammatory cytokines, apoptosis-related molecules, and markers of adverse ventricular remodeling was measured using RT-PCR and Western blot.
Treatment with ()-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid significantly improved cardiac function, in particular by increasing /. Simultaneously, the expression of the proinflammatory cytokines TNF- and IL-1 was markedly reduced in the treatment group compared with the MI group. In addition, ()-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid-treated tissues displayed decreased expression of Bax, caspase-3, and caspase-9 and increased expression of Bcl-2, which was in part due to the promotion of Akt phosphorylation.
These data demonstrated that ()-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid possesses potent cardioprotective effects against cardiac injury in a rat model of heart failure, which is mediated, at least in part, by suppression of the inflammatory and cell apoptosis responses.
尽管已经有许多研究致力于阐明心力衰竭的分子机制，但仍未开发出有效的药理学疗法来保护心脏组织免受急性心肌梗死（MI）后严重的收缩功能丧失。
我们在心力衰竭大鼠模型中研究了（）-2-乙酰氧基-3-（3,4-二羟基苯基）丙烯酸作为一种具有强大抗氧化和抗细胞凋亡活性的新型化合物的心脏保护作用。在 MI 后 6 周，以不同剂量（15、30 和 60mg/kg）向大鼠系统给予（）-2-乙酰氧基-3-（3,4-二羟基苯基）丙烯酸。通过血流动力学测量评估心脏功能。使用 RT-PCR 和 Western blot 测量促炎细胞因子、凋亡相关分子和不良心室重构标志物的表达。
（）-2-乙酰氧基-3-（3,4-二羟基苯基）丙烯酸治疗显著改善了心脏功能，特别是通过增加。同时，与 MI 组相比，治疗组中促炎细胞因子 TNF-和 IL-1 的表达明显降低。此外，（）-2-乙酰氧基-3-（3,4-二羟基苯基）丙烯酸处理的组织 Bax、caspase-3 和 caspase-9 的表达降低，Bcl-2 的表达增加，这部分归因于 Akt 磷酸化的促进。
这些数据表明，（）-2-乙酰氧基-3-（3,4-二羟基苯基）丙烯酸对心力衰竭大鼠模型中的心脏损伤具有强大的心脏保护作用，至少部分通过抑制炎症和细胞凋亡反应来介导。
