College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Zhengzhou, China.
Pharm Biol. 2020 Dec;58(1):597-609. doi: 10.1080/13880209.2020.1778043.
In the antihypertensive study of phenylacetamide (PA) on spontaneously hypertensive rats (SHR), it was occasionally found that PA prevents myocardial injury. Clarify the protective mechanism of PA on myocardial injury in SHR rats. , SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). , H9c2 cells were treated with PA (1, 5, 10 μM) for 24 h, and then stimulated with HO (300 μM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers. , PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1β) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-β pathway (Smad3) better. , PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression. PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.
在苯乙酰胺（PA）对自发性高血压大鼠（SHR）的降压研究中，偶尔发现 PA 可预防心肌损伤。阐明 PA 对 SHR 大鼠心肌损伤的保护机制。将 SHR 大鼠分为对照组和给药组，每组 12 只。给药组分别给予 15、30、45mg/kgPA 连续灌胃 3 周。给予 H9c2 细胞不同浓度的 PA（1、5、10μM）预处理 24h 后，用 300μM HO 刺激 4h。通过心肌病理、心功能和生化标志物等方面探讨分子机制。结果表明，PA（15、30、45mg/kg）可降低 CVF 从 14.8±1.62 到 9.94±1.56、8.6±1.33、8.14±1.45%；提高 LVEF 相对水平从 0.8±0.06 到 0.83±0.04、0.86±0.05、0.9±0.04。三种剂量均可改善心脏病理结构和功能（LVEDD、LVESD、LVFS、心指数、NT-proBNP、CKMB、SBP），但以 45mg/kg 效果最佳。但不同剂量显示出不同的分子机制。PA（15mg/kg）改善 RAAS 系统（REN、ACE）、炎症（ET-1、IL-1β）和 MAPK 途径（p-ERK/ERK、p-JNK/JNK）更好。PA（45mg/kg）改善氧化应激（SOD、NOX1）和 TGF-β 途径（Smad3）更好。PA 改善细胞活力、氧化应激（SOD、NOX1）和 Smad3 蛋白表达。PA 在不同浓度下通过调节不同的机制改善心肌损伤，高剂量效果最佳。该实验为开发心血管疾病新的临床药物提供了理论依据。
