Department of Physiology, Bengbu Medical College, Bengbu 233030, Anhui, China.
Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Bengbu Medical College, Bengbu 233030, Anhui, China.
Exp Biol Med (Maywood). 2022 Sep;247(17):1591-1600. doi: 10.1177/15353702221110646. Epub 2022 Jul 14.
Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.
没食子酸表没食子儿茶素酯 (EGCG) 在多种组织中具有抗纤维化作用；然而，EGCG 对糖尿病引起的心肌纤维化影响的分子机制尚不清楚。本研究旨在揭示 EGCG 对 2 型糖尿病大鼠心脏的抗纤维化作用，并探讨其分子机制。大鼠随机分为以下四组：正常组（NOR）、糖尿病心肌病组（DCM）、DCM+40mg/kg EGCG 组和 DCM+80mg/kg EGCG 组。EGCG 治疗 8 周后，测定空腹血糖、左心室血流动力学指标、心脏指数和心肌损伤相关参数。苏木精和伊红染色和天狼星红染色用于评估心肌病理改变和胶原积累。测定心肌羟脯氨酸、胶原-I、胶原-III、转化生长因子 (TGF)-β1、基质金属蛋白酶 (MMP)-2 和 MMP-9 的含量。检测心肌 TGF-β1、MMP-2 和 MMP-9 的基因表达水平。测定腺苷 5'-单磷酸激活蛋白激酶 (AMPK) 和雷帕霉素靶蛋白 (mTOR) 等自噬调节剂以及微管相关蛋白-1 轻链 3 和 Beclin1 等自噬标志物的含量。结果表明，糖尿病显著降低了心脏的收缩功能，加重了心肌肥大和损伤。此外，糖尿病抑制了心肌组织中自噬的激活，促进了心脏纤维化。摄入不同剂量的 EGCG 后，心肌收缩功能障碍、肥大和损伤得到改善；EGCG 治疗组心肌自噬被激活，心肌纤维化减轻。总之，这些发现表明 EGCG 可减轻 2 型糖尿病大鼠的心肌纤维化，其作用机制与通过调节 AMPK/mTOR 通路激活自噬，进而抑制 TGF-β/MMPs 通路有关。
