BACKGROUND Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.

中文翻译：

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丹酚酸B通过抑制IGFBP3改善糖尿病性心肌病的心肌功能。

背景技术丹酚酸B（Sal B）是来自丹参丹参干根和根茎的酚酸的代表性成分。（唇形科），已被广泛用于治疗心脑血管疾病。但是，尚不清楚Sal B对糖尿病性心肌病（DCM）的作用。方法通过链脲佐菌素（STZ）处理在C57BL / 6 J小鼠中诱发1型糖尿病，同时腹膜内注射Salvianolic Acid B（Sal B（15或30 mg / kg / d）），持续16周。在此期间，通过超声心动图评估心脏功能，并通过Masson三色和Picrosirius Red染色评估总胶原沉积。暴露于低氧的人脐静脉内皮细胞用于研究不同剂量的Sal B对体外血管生成和管形成的影响。进行转录组测序以鉴定Sal B的潜在靶点。结果Sal B改善了左心室功能障碍和重塑，并减少了糖尿病小鼠心脏中的胶原沉积。Sal B的给药以剂量依赖性方式增加了血管内皮生长因子（VEGF）受体2（VEGFR2）和VEGFA的表达，并在体内和体外促进了血管生成。此外，Sal B降低了HG诱导的胰岛素样生长因子结合蛋白3（IGFBP3）的表达，诱导了细胞外信号调节蛋白激酶和蛋白激酶B（AKT）的磷酸化，增强了细胞增殖，并激活了内皮细胞中的VEGFR2 / VEGFA信号传导。潜在的机制涉及SalB增强缺氧下HUVEC中IGFBP3启动子DNA甲基化并诱导IGFBP3核易位。结论Sal B通过抑制IGFBP3促进DCM中的血管生成，减轻心脏纤维化和心脏重塑。