Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
J Mol Cell Cardiol. 2020 Feb;139:98-112. doi: 10.1016/j.yjmcc.2020.01.009. Epub 2020 Jan 23.
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.
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.
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.
Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.
丹酚酸 B（Sal B）是从丹参（唇形科）的干根和根茎中提取的酚酸的代表性成分，已广泛用于治疗心血管和脑血管疾病。然而，Sal B 对糖尿病心肌病（DCM）的影响尚不清楚。
用链脲佐菌素（STZ）处理 C57BL/6 J 小鼠诱导 1 型糖尿病，同时腹腔注射丹酚酸 B（Sal B（15 或 30mg/kg/d）16 周。在此期间结束时，通过超声心动图评估心脏功能，并通过 Masson 三色和苦味酸天狼猩红染色评估总胶原沉积。用人脐静脉内皮细胞（HUVEC）在缺氧条件下，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。
Sal B 改善了糖尿病小鼠的左心室功能障碍和重构，并减少了心脏中的胶原沉积。Sal B 呈剂量依赖性增加血管内皮生长因子受体 2（VEGFR2）和血管内皮生长因子 A（VEGFA）的表达，并在体内和体外促进血管生成。此外，Sal B 降低了高糖诱导的胰岛素样生长因子结合蛋白 3（IGFBP3）的表达，诱导细胞外信号调节蛋白激酶和蛋白激酶 B（AKT）的磷酸化，增强细胞增殖，并激活内皮细胞中的 VEGFR2/VEGFA 信号通路。潜在机制涉及 SalB 在缺氧条件下增强 IGFBP3 启动子 DNA 甲基化并诱导 IGFBP3 的核易位。
Sal B 通过抑制 IGFBP3 促进血管生成并减轻 DCM 中的心肌纤维化和心肌重构。
