白芷乙醇提取物通过激活糖尿病患者的血管生成来改善受损的伤口愈合。

Angelica Dahurica ethanolic extract improves impaired wound healing by activating angiogenesis in diabetes.

作者信息

Zhang Xiao-Na, Ma Ze-Jun, Wang Ying, Sun Bei, Guo Xin, Pan Cong-Qing, Chen Li-Ming

机构信息

From the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

From 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development, Ministry of Health, Metabolic Disease Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People's Republic of China.

出版信息

PLoS One. 2017 May 24;12(5):e0177862. doi: 10.1371/journal.pone.0177862. eCollection 2017.

Abstract

Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation. The angiogenic property of ADEE was subsequently verified ex vivo using aortic ring assays. Furthermore, we investigated the in vitro angiogenic activity of ADEE and its underlying mechanisms using human umbilical vein endothelial cells. ADEE treatment induced HUVECs proliferation, migration, and tube formation, which are typical phenomena of angiogenesis, in dose-dependent manners. These effects were associated with activation of angiogenic signal modulators, including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, endothelial nitric oxide synthase (eNOS) as well as increased NO production, and independent of affecting VEGF expression. ADEE-induced angiogenic events were inhibited by the MEK inhibitor PD98059, the PI3K inhibitor Wortmannin, and the eNOS inhibitor L-NAME. Our findings highlight an angiogenic role of ADEE and its ability to protect against impaired wound healing, which may be developed as a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.

摘要

异常血管生成在糖尿病患者伤口愈合受损及慢性伤口形成过程中发挥着重要作用。白芷是一种具有广泛药用功效的常见传统中药。在本研究中,我们利用链脲佐菌素诱导的糖尿病大鼠,分析了白芷乙醇提取物(ADEE)在纠正糖尿病患者血管生成受损及伤口愈合延迟方面的潜在作用。ADEE治疗通过诱导血管生成和肉芽组织形成,加速了糖尿病伤口的愈合。随后,通过主动脉环试验在体外验证了ADEE的血管生成特性。此外,我们利用人脐静脉内皮细胞研究了ADEE的体外血管生成活性及其潜在机制。ADEE处理以剂量依赖的方式诱导人脐静脉内皮细胞增殖、迁移和管腔形成,这些都是血管生成的典型现象。这些作用与血管生成信号调节因子的激活有关,包括细胞外信号调节激酶1/2(ERK1/2)、Akt、内皮型一氧化氮合酶(eNOS)以及一氧化氮生成增加,且与影响血管内皮生长因子(VEGF)表达无关。MEK抑制剂PD98059、PI3K抑制剂渥曼青霉素和eNOS抑制剂L-NAME可抑制ADEE诱导的血管生成事件。我们的研究结果突出了ADEE的血管生成作用及其预防伤口愈合受损的能力,这可能会发展成为一种治疗糖尿病患者血管生成受损和伤口愈合延迟的有前景的疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fb/5443501/62646052c42c/pone.0177862.g001.jpg

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