Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China.
Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China.
Cell Biol Int. 2019 Jan;43(1):65-72. doi: 10.1002/cbin.11079.
Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality in diabetes mellitus (DM) patients. Previous studies have shown that the transforming growth factor-beta 1 (TGF-β1)/Smad signaling pathway plays a key role in the development of myocardial fibrosis in DCM. Silymarin (SMN) is used clinically to treat liver disorders and acts by influencing TGF-β1. However, the possible effects of silymarin on DCM remain to be elucidated. In our study, the DM animal model was induced by streptozotocin (STZ) injection. Fasting blood glucose level was measured, and the structure and function of the heart were measured by hematoxylin and eosin (H&E) and Masson staining, echocardiography, and transmission electron microscopy (TEM). Western blot was used to detect the expression of TGF-β1, Smad2/3, phosphorylation Smad2/3(p-Smad2/3), and Smad7. Our results showed that silymarin downregulated blood glucose level and significantly improved cardiac fibrosis and collagen deposition in DM rats detected by H&E, Masson staining, and TEM assays. The echocardiography results showed that silymarin administration attenuated cardiac dysfunction in DM rats. Additionally, compared with untreated DM rats, levels of TGF-β1 and p-Smad2/3 were decreased, whereas Smad7 was increased following silymarin administration. These data demonstrate that silymarin ameliorates DCM through the inhibition of TGF-β1/Smad signaling, suggesting that silymarin may be a potential target for DCM treatment.
糖尿病心肌病（DCM）是糖尿病（DM）患者发病率和死亡率的主要原因。先前的研究表明，转化生长因子-β1（TGF-β1）/Smad 信号通路在 DCM 中心肌纤维化的发展中起关键作用。水飞蓟素（SMN）临床上用于治疗肝脏疾病，通过影响 TGF-β1 发挥作用。然而，水飞蓟素对 DCM 的可能影响仍有待阐明。在我们的研究中，通过链脲佐菌素（STZ）注射诱导 DM 动物模型。测量空腹血糖水平，并通过苏木精和伊红（H&E）和 Masson 染色、超声心动图和透射电子显微镜（TEM）测量心脏的结构和功能。Western blot 用于检测 TGF-β1、Smad2/3、磷酸化 Smad2/3（p-Smad2/3）和 Smad7 的表达。我们的结果表明，水飞蓟素降低了血糖水平，并通过 H&E、Masson 染色和 TEM 检测显著改善了 DM 大鼠的心脏纤维化和胶原沉积。超声心动图结果表明，水飞蓟素可减轻 DM 大鼠的心脏功能障碍。此外，与未治疗的 DM 大鼠相比，水飞蓟素给药后 TGF-β1 和 p-Smad2/3 水平降低，而 Smad7 水平升高。这些数据表明，水飞蓟素通过抑制 TGF-β1/Smad 信号通路改善 DCM，表明水飞蓟素可能是 DCM 治疗的潜在靶点。
