The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3^′-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.

中文翻译：

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丹酚酸 B 通过上调 miR-486a-5p 表达减轻高糖诱导的血管平滑肌细胞炎症

糖尿病的大血管并发症导致 2 型糖尿病 (T2DM) 患者的高死亡率和致残率。血管平滑肌细胞（VSMC）的炎症反应贯穿其病理生理过程。丹酚酸 B (Sal B) 对心血管系统具有有益作用。然而，其在糖尿病血管炎症反应中的作用和机制仍不清楚。在这项研究中，我们发现 Sal B 可以减轻糖尿病小鼠的血管炎症和高葡萄糖 (HG) 诱导的 VSMC 炎症。随后，我们发现 Sal B 通过下调 FOXO1 来减少 HG 诱导的 VSMC 炎症。此外，HG 处理的 VSMC 中 miR-486a-5p 表达明显降低。 Sal B 通过上调 miR-486a-5p 减轻 HG 诱导的 VSMC 炎症。功能丧失和获得实验证明，miR-486a-5p模拟物的转染抑制了HG诱导的VSMC炎症，而miR-486a-5p抑制剂的转染促进了HG诱导的VSMC炎症，从而改善了糖尿病小鼠的血管炎症。此外，研究表明miR-486a-5p通过直接靶向FOXO1的3'-UTR来抑制FOXO1的^表达。总之，Sal B通过上调miR-486a-5p并加重其对FOXO1表达的抑制来减轻VSMC的炎症反应。 Sal B 通过调节 miR-486a-5p/FOXO1 轴，在 HG 诱导的 VSMC 炎症中发挥显着的抗炎作用。