局部应用不同浓度硝普钠对创伤愈合影响的时效性研究

The chronergy study on the influence of topical application of sodium nitroprusside in different concentrations on the wound healing

目的:应用组织化学及计算机辅助图像分析方法,观察外源性一氧化氮(nitricoxide,NO)在创伤愈合过程不同时间对肉芽组织生长及成纤维细胞增殖的影响,探讨其对促进创伤愈合和抑制病理性瘢痕形成的机制。方法:60只大鼠随机分为对照组及实验A、B、C、D组,每组12只,通过建立大鼠创伤模型,并分别在创面局部应用5%葡萄糖溶液、0.5mmol/L、1mmol/L、2mmol/L和4mmol/L硝普钠,观察及测量创伤后3天、7天、10天和14天的肉芽生长情况、成纤维细胞数密度、胶原纤维面密度和肉芽组织中羟脯氨酸含量。结果:实验A、B组相对于对照组和实验C、D组表现出更好的伤口愈合,且瘢痕形成最小。结论:局部应用外源性NO具有显著的促修复作用,主要体现在伤后第7～10天,小剂量的NO促进创面愈合的作用远远大于大剂量NO。局部过量的NO聚积可阻碍正常的伤口愈合,并呈现全身毒性反应。在伤后7～10天应用外源性NO可抑制病理性瘢痕形成。

Objective By using histochemistry and computer-assisted image analysis, the influence of exogenous nitric oxide on the growth of granulation tissue and the fibroblasts proliferation in the series periods of healing are observed. To discuss the mechanism of exogenous nitric oxide on promoting the wound healing and inhibiting the formation of hypertrophic scar and keloid tissue. Methods 60 rats are divided into 5 groups randomly, that is the control group and the treatment group A, B, C, D. There are 12 rats involved in each group. By setting up the rat wound model and topically injecting 5% glucose solution, 0.5mmol/L SNP, lmmol/L SNP, 2mmol/L SNP and 4mmol/L SNP respectively into the wound, the granulation tissue formation, the fibroblasts numerical density on area （NA）, the collagen fibers area density on area （AA） and the content of hydroxyproline in the granulation on the day of 3 days, 7 days, 10 days and 14 days after injury are observed and surveied respectively. Results The treatment group A and B shows better wound healing and smaller formation of hypertrophic scar and keloid tissue than the control group and the treatment group C and D. Conclusion Exogenous NO applied topically can promote the reparation course remarkably which affects the day of 7 days to 10 days after injury mostly. Smaller dose of exogenous NO shows much better effectiveness on promoting the wound healing than larger dose NO. Overdose NO accumulations at topical wound can delay a normal healing and induce general toxicity reaction. By using some exogenous NO at 7 days to 10 days post-injury, the pathological scarring could be suppressed.