Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, 130033, China.
Department of Hepatobiliary and Pancreatic Surgery, First Hospital, Jilin University, Changchun, China.
Peptides. 2018 Jan;99:27-35. doi: 10.1016/j.peptides.2017.10.018. Epub 2017 Nov 4.
Ghrelin, a growth hormone-releasing peptide, potentially improves cardiac function, but the mechanisms remain unclear. In the study, the rat heart failure (HF) model was established by ligating the left anterior descending coronary artery (LAD) and treated with ghrelin (100μg/kg, subcutaneous injection, bid); neonatal rat cardiomyocytes were cultured and stimulated with Ang II (0.1μM) and ghrelin(0.1μM) to explore the underlying mechanism of ghrelin in myocardial remodeling. Hemodynamic changes and serum brain natriuretic peptide (BNP) concentrations were measured to assess cardiac function. Left ventricular mass index (LVMI), hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were performed to evaluate myocardial fibrosis. Interestingly, ghrelin significantly improved cardiac function by inhibiting fibrous tissue proliferation. To further explore the mechanisms by which ghrelin interferes with myocardial fibrosis, the levels of activin A (Act A) and its blocker-follistatin (FS) were examined by immunohistochemistry; Act A levels were significantly increased in the myocardial infarction (MI), and ghrelin administeration downregulated Act A expression. In contrast, FS expression showed no significant change in all experimental groups. Furthermore, ghrelin decreased Ang II-induced Act A expression with no effect on FS expression in primary rat cardiomyocytes in vitro (real-time quantitative PCR and ELISA). Thus, ghrelin corrected the Act A/FS imbalance. Finally, Act A treated cultured primary rat cardiac fibroblasts (CFs) showed increased proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay] and enhanced expressions of type I and type III collagen (Col I and Col III) (real-time quantitative PCR). These data suggest that ghrelin inhibits myocardial fibrosis, attenuates left ventricular remodeling, and eventually improves cardiac function by adjusting Act A/FS imbalance.
胃饥饿素是一种生长激素释放肽，可能改善心脏功能，但机制尚不清楚。在该研究中，结扎大鼠左前降支冠状动脉（LAD）建立心力衰竭（HF）模型，并给予胃饥饿素（100μg/kg，皮下注射，每日 2 次）治疗；培养新生大鼠心肌细胞并用血管紧张素 II（Ang II，0.1μM）和胃饥饿素（0.1μM）刺激，以探讨胃饥饿素在心肌重构中的潜在作用机制。测量血流动力学变化和血清脑钠肽（BNP）浓度来评估心脏功能。左心室质量指数（LVMI）、苏木精和伊红（H&E）染色以及Masson 三色染色评估心肌纤维化。有趣的是，胃饥饿素通过抑制纤维组织增殖显著改善心脏功能。为了进一步探讨胃饥饿素干扰心肌纤维化的机制，通过免疫组化检测激活素 A（Act A）及其阻滞剂卵泡抑素（FS）的水平；心肌梗死（MI）中 Act A 水平显著升高，胃饥饿素给药下调 Act A 表达。相比之下，所有实验组 FS 表达均无明显变化。此外，胃饥饿素降低了 Ang II 诱导的原代大鼠心肌细胞中 Act A 的表达，而对 FS 表达无影响（实时定量 PCR 和 ELISA）。因此，胃饥饿素纠正了 Act A/FS 失衡。最后，Act A 处理培养的原代大鼠心脏成纤维细胞（CFs）显示增殖增加[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定]和Ⅰ型和Ⅲ型胶原（Col I 和 Col III）表达增强（实时定量 PCR）。这些数据表明，胃饥饿素通过调节 Act A/FS 失衡抑制心肌纤维化，减轻左心室重构，最终改善心脏功能。
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