CONTEXT Cryptotanshinone (CT) is a diterpene quinone compound from Salvia miltiorrhiza Bge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds. OBJECTIVE This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice. MATERIALS AND METHODS Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measured in vitro with human umbilical vein endothelial cells (HUVECs). RESULTS CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS. In vitro, CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9. CONCLUSIONS Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.

中文翻译：

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隐丹参酮通过对炎症、血管生成和细胞外基质重塑的调节作用促进 2 型糖尿病的伤口愈合

背景 隐丹参酮 (CT) 是一种来自丹参的二萜醌化合物。唇形科已广泛用于心脑血管疾病，可能对治疗糖尿病伤口有效。目的 本研究通过在 db/db 小鼠中采用切除伤口夹板模型来评估 CT 的伤口愈合活性。材料和方法 在非糖尿病 (db/+) 和糖尿病 (db/db) 小鼠的背部诱导伤口，并用羧甲基纤维素钠 (CMC-Na) 或 300 mg/kg/d CT 治疗 16 天。每两天测量一次伤口闭合。分析了体重、空腹血糖、再上皮化、肉芽形成、白细胞浸润、毛细血管密度、胶原沉积和 CXCL1、CXCL2、VEGF、Ang-1、p-eNOS、eNOS、α-SMA、MMP2 和 MMP9 的表达。用人脐静脉内皮细胞 (HUVEC) 在体外测量 VEGF 的表达和管形成。结果 CT 显着加快伤口闭合速度，因为在受伤后第 16 天收缩率从 68%（未治疗组）增加到 83%（CT 治疗组）。观察到上皮再形成和肉芽组织形成显着增加。从机制上讲，CT 抑制白细胞浸润和 CXCL1 和 CXCL2 表达。CT 治疗还增加了血管密度和 VEGF、Ang-1 和 p-eNOS 的表达水平。在体外，CT 增强了 VEGF 的表达和内皮细胞的管形成。此外，CT 通过促进成纤维细胞转化和抑制 MMP2 和 MMP9 来增强细胞外基质 (ECM) 重塑。