姜黄素诱导的血管生成加速糖尿病大鼠伤口愈合。
Curcumin-induced angiogenesis hastens wound healing in diabetic rats.
作者信息
Kant Vinay, Gopal Anu, Kumar Dhirendra, Pathak Nitya N, Ram Mahendra, Jangir Babu L, Tandan Surendra K, Kumar Dinesh
机构信息
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, UP, India.
Division of Veterinary Pathology, Indian Veterinary Research Institute, Izatnagar, UP, India.
出版信息
J Surg Res. 2015 Feb;193(2):978-88. doi: 10.1016/j.jss.2014.10.019. Epub 2014 Oct 18.
BACKGROUND
Neovasculogenesis, vital for wound healing, gets compromised in diabetics patients, which consequently delayed wound healing. Previous studies have shown curcumin as both a stimulatory and an inhibitory agent in the neovasculogenesis process. So, present study was aimed to investigate the effects of curcumin on wound healing in diabetic rats and to explore the expressions of the various factors involved in neovasculogenesis.
MATERIALS AND METHODS
Open excisional diabetic wound was created in sixty rats and divided into three groups viz. i) control, ii) pluronic gel-treated, and iii) curcumin-treated. The pluronic F-127 gel (25%) and curcumin (0.3%) in the pluronic gel were topically applied once daily for 19 d. The wound healing and neovasculogenesis among these groups were evaluated by gross appearance of wounds and microscopically by hematoxylin and eosin staining, immunohistochemistry for CD31, messenger RNA expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, hypoxia-inducible growth factor-1 alpha, stromal cell-derived growth factor-1 alpha, and heme oxygenase-1, and Western blotting studies of VEGF and TGF-β1 in granulation and/or healing tissue on days 3, 7, 14, and 19.
RESULTS
Curcumin application caused markedly fast wound closure with well-formed granulation tissue dominated by fibroblast proliferation, collagen deposition, and complete early regenerated epithelial layer. Immunohistochemistry for CD31 revealed well-formed blood vessels with increased microvessel density on days 3, 7, and 14 in the curcumin-treated group. Expressions of VEGF and TGF-β1 on days 3, 7, and 14, hypoxia-inducible growth factor-1 alpha, stromal cell-derived growth factor-1 alpha, and heme oxygenase-1 on days 3 and 7 were increased in curcumin-treated diabetic rats, as compared with other groups.
CONCLUSIONS
Curcumin enhanced the neovasculogenesis and accelerated the wound healing in diabetic rats by increased expressions of various factors.
背景
新生血管形成对伤口愈合至关重要，而糖尿病患者的新生血管形成受损，从而导致伤口愈合延迟。先前的研究表明姜黄素在新生血管形成过程中既是刺激剂又是抑制剂。因此，本研究旨在探讨姜黄素对糖尿病大鼠伤口愈合的影响，并探索参与新生血管形成的各种因子的表达。
材料与方法
在60只大鼠身上制造开放性切除性糖尿病伤口，并将其分为三组，即：i）对照组，ii）普朗尼克凝胶治疗组，iii）姜黄素治疗组。每天一次局部应用25%的普朗尼克F-127凝胶和含0.3%姜黄素的普朗尼克凝胶，持续19天。通过伤口的大体外观以及苏木精和伊红染色、CD31免疫组织化学、血管内皮生长因子（VEGF）、转化生长因子（TGF）-β1、缺氧诱导生长因子-1α、基质细胞衍生生长因子-1α和血红素加氧酶-1的信使核糖核酸表达，以及在第3、7、14和19天对肉芽组织和/或愈合组织中的VEGF和TGF-β1进行蛋白质印迹研究，来评估这些组之间的伤口愈合和新生血管形成情况。
结果
应用姜黄素导致伤口明显快速闭合，形成良好的肉芽组织，其主要特征为成纤维细胞增殖、胶原沉积和早期完全再生的上皮层。CD31免疫组织化学显示，在姜黄素治疗组中，第3、7和14天微血管密度增加，血管形成良好。与其他组相比，姜黄素治疗的糖尿病大鼠在第3、7和14天VEGF和TGF-β1的表达，以及在第3和7天缺氧诱导生长因子-1α、基质细胞衍生生长因子-1α和血红素加氧酶-1的表达均增加。
结论
姜黄素通过增加各种因子的表达，增强了糖尿病大鼠的新生血管形成并加速了伤口愈合。
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