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Cardioprotective Effect of (Z)-2-Acetoxy-3-(3,4-Dihydroxyphenyl) Acrylic Acid: Inhibition of Apoptosis in Cardiomyocytes.
Cardiovascular Therapeutics ( IF 3.1 ) Pub Date : 2020-05-01 , DOI: 10.1155/2020/8584763
Wei Guo 1 , Zhijun Wang 1 , Hao Jue 1 , Chunnan Dong 1 , Cheng Yang 2
Affiliation  

Background. 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. Methods. We examined the cardioprotective effects of (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid, a new compound with potent antioxidant and antiapoptotic activities in a rat model of heart failure. (Z)-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. Results. Treatment with (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid significantly improved cardiac function, in particular by increasing . Simultaneously, the expression of the proinflammatory cytokines TNF-α and IL-1β was markedly reduced in the treatment group compared with the MI group. In addition, (Z)-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. Conclusion. These data demonstrated that (Z)-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.

中文翻译:

(Z)-2-Acetoxy-3-(3,4-Dihydroxyphenyl) Acrylic Acid 的心脏保护作用:抑制心肌细胞凋亡。

背景。尽管已经进行了许多研究来阐明心力衰竭的分子机制,但尚未开发出一种有效的药物疗法来保护心脏组织免受与急性心肌梗死 (MI) 后心力衰竭相关的收缩功能的严重丧失。方法。我们检查了 ( Z )-2-acetoxy-3-(3,4-dihydroxyphenyl) 丙烯酸的心脏保护作用,这是一种在心力衰竭大鼠模型中具有强效抗氧化和抗凋亡活性的新化合物。( Z)-2-Acetoxy-3-(3,4-dihydroxyphenyl) 丙烯酸在 MI 后 6 周以不同剂量(15、30 和 60 mg/kg)全身性给药至大鼠。通过血流动力学测量评估心脏功能。使用 RT-PCR 和蛋白质印迹测量促炎细胞因子、凋亡相关分子和不良心室重构标志物的表达。结果。( Z )-2-acetoxy-3-(3,4-dihydroxyphenyl) 丙烯酸治疗显着改善心脏功能,特别是通过增加. 同时,与MI组相比,治疗组促炎细胞因子TNF - α和IL-1β的表达明显降低。此外,( Z )-2-acetoxy-3-(3,4-dihydroxyphenyl) 丙烯酸处理的组织显示出 Bax、caspase-3 和 caspase-9 的表达降低,而 Bcl-2 的表达增加。部分是由于促进了 Akt 磷酸化。结论。这些数据表明,( Z )-2-acetoxy-3-(3,4-dihydroxyphenyl) 丙烯酸在心力衰竭大鼠模型中对心脏损伤具有有效的心脏保护作用,至少部分是通过抑制炎症反应和细胞凋亡反应。
更新日期:2020-05-01
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