Kant Vinay, Kumar Dinesh, Prasad Raju, Gopal Anu, Pathak Nitya N, Kumar Pawan, Tandan Surender K
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
J Surg Res. 2017 May 15;212:130-145. doi: 10.1016/j.jss.2017.01.011. Epub 2017 Jan 28.
Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocin-induced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats.
Open cutaneous excision wound was created on the back of each of the 60 diabetic rats. Wound-inflicted rats were equally divided into three groups namely, control, gel treated, and SP + curcumin treated. Normal saline, pluronic gel, and SP (0.5 × 10M) + curcumin (0.15%) were topically applied once daily for 19 d to these control, gel-treated, and SP + curcumin groups, respectively.
SP + curcumin combination significantly accelerated wound closure and decreased messenger RNA expressions of tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell-derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase, and activities of superoxide dismutase, catalase, and glutathione peroxidase in granulation-healing tissue, compared with control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth-associated protein 43-positive nerve fibers, and thick regenerated epithelial layer.
The combination of SP and curcumin accelerated wound healing in diabetic rats and both the drugs were compatible at the doses used in this study.
我们早期的研究表明，在链脲佐菌素诱导的糖尿病大鼠切除皮肤伤口上局部应用P物质（SP）或姜黄素可加速伤口愈合。在本研究中，我们旨在评估SP和姜黄素联合应用对糖尿病大鼠伤口愈合的潜力。
在60只糖尿病大鼠的背部制造开放性皮肤切除伤口。将造伤大鼠平均分为三组，即对照组、凝胶治疗组和SP +姜黄素治疗组。分别对这些对照组、凝胶治疗组和SP +姜黄素组每天一次局部应用生理盐水、普朗尼克凝胶和SP（0.5×10M）+姜黄素（0.15%），持续19天。
与对照组和凝胶治疗组相比，SP +姜黄素联合应用显著加速了伤口闭合，降低了肿瘤坏死因子-α、白细胞介素-1β和基质金属蛋白酶-9的信使核糖核酸表达，而联合应用显著增加了肉芽组织愈合组织中白细胞介素-10、血管内皮生长因子、转化生长因子-β1、缺氧诱导因子1-α、基质细胞衍生因子-1α、血红素加氧酶-1和内皮型一氧化氮合酶的表达，以及超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。在联合组中，肉芽组织更好，这通过成纤维细胞增殖、胶原沉积、微血管密度、生长相关蛋白43阳性神经纤维和增厚的再生上皮层得到证实。
SP和姜黄素联合应用加速了糖尿病大鼠的伤口愈合，并且在本研究中使用的剂量下两种药物是相容的。
