Sodium Tanshinone IIA sulfonate improves post-ischemic angiogenesis in hyperglycemia
Sodium Tanshinone IIA sulfonate improves post-ischemic angiogenesis in hyperglycemia
复制标题
丹参酮 IIA 磺酸钠改善高血糖时缺血后血管生成
DOI：
10.1016/j.bbrc.2019.09.106
复制
发表时间：
2019-12-10
影响因子：
3.1
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Chen, Lingdan;He, Wenjun;Wang, Tao
背景资料：糖尿病是外周动脉疾病（PAD）的重要危险因素，也会导致缺血肢体的灌注恢复受损，最终导致PAD患者的预后不良。丹参酮IIA磺酸钠（STS）是一种来自草药的单体，已被证明可以改善包括心肌梗死在内的各种缺血性疾病的结局。方法和结果：结扎小鼠单侧股动脉作为实验性PAD模型，STS治疗改善灌注恢复，增加毛细血管密度，降低活性氧（ROS）水平和microRNA-133 a（miR-133 a）在糖尿病小鼠缺血后肢中的表达;然而，STS没有改变非糖尿病C57 BL/6小鼠的灌注恢复。糖尿病小鼠股动脉结扎后7 d取缺血肌肉组织进行生化检测，STS可降低MDA，升高GCH 1和cGMP水平。此外，STS治疗增加了从糖尿病小鼠的缺血肌肉组织分离的内皮细胞中的miR-133 a表达。在高糖培养的内皮细胞中，STS增加模拟缺血条件下的管形成和一氧化氮（NO）产生，并降低细胞ROS水平和miR-133 a表达。此外，使用外源性microRNA的GCH 1抑制剂或miR-133 a过表达模拟了高血糖和缺氧条件下培养的内皮细胞中STS诱导的血管生成效应和活性氧中和作用。结论：这些发现表明STS通过抑制miR-133 a表达和增加GCH-1蛋白水平来改善糖尿病实验性PAD中的血管生成。(C)2019爱思唯尔公司All rights reserved.
Background: Diabetes is a strong risk factor of peripheral arterial disease (PAD), and also leads to impaired perfusion recovery in the ischemic limb, which eventually results in poor outcomes in PAD patients. Sodium Tanshinone IIA Sulfonate (STS), a monomer from herbs, has been shown to improve the outcomes in a variety of ischemic disease including myocardial infarction. However, the effects of STS treatment in PAD is not known.Methods and results: Unilateral femoral artery was ligated in mice as experimental PAD models, STS treatment improved perfusion recovery, increased capillary densities, decreased reactive oxygen species (ROS) level and microRNA-133a (miR-133a) expression in the ischemic hindlimb in diabetic mice; however, STS did not change perfusion recovery in non-diabetic C57BL/6 mice. Ischemic muscle tissue from diabetic mice was harvested 7 days after femoral ligation for biochemical test, STS resulted in reduced malondialdehyde (MDA), and increased GTP cyclohydrolase 1 (GCH1) and cyclic guanine monophosphate (cGMP) levels. In addition, STS treatment increased miR-133a expression in endothelial cells isolated from ischemic muscle tissue of diabetic mice. In endothelial cells cultured in high glucose medium, STS increased tube formation and nitric oxide (NO) production, and reduced cellular ROS level and miR-133a expression under simulated ischemic condition. In addition, GCH1 inhibitor or miR-133a overexpression using exogenous microRNA mimic blunted STS-induced angiogenic effects and ROS neutralization in cultured endothelial cells under hyperglycemic and hypoxic conditions.Conclusion: These findings demonstrate STS improves angiogenesis via inhibiting miR-133a expression and increasing GCH-1 protein levels in experimental PAD with diabetes. (C) 2019 Elsevier Inc. All rights reserved.