低浓度尼古丁胶原膜缓释微粒系统促进大鼠硬腭黏膜创伤愈合的研究

摘要

Objective Studies have shown that low concentrations of nicotine can promote neovascularization and promote wound healing.This article aimed to investigate the influence of low concentration collagen membrane slow-release system on the hard palate trauma of rats.Methods Using poly(lactic acid-co-glycolic acid) (PLGA) copolymer as carrier materials, low concentration nicotine sustained-release particles were prepared by emulsion evaporation method (w/o/w), using collagen membrane as the brace and establish a low concentration collagen membrane system.48 Wistar rats were divided into experimental group and blank group, 3 mm diameter circular wound was made in the forepart palate.Low concentration of nicotine collagen membrane sustained-release particle system and blank collagen membrane (control) were sutured on the wound with 6-0 absorbable thread.Then, observed the wound healing of 0, 3, 7, 10 days and compared the healing differences between each groups.Results Under the electron microscope, the nicotine sustained-release particles were circular, similar size with rough surface, the average diameter were 3.0±0.2μm, the encapsulation efficiency and drug loading rate was 50.2% and 4.12% respectively.In vitro, nicotine sustained-release particles released much more nicotine on the first day, less on the second day, tends to stable and fluctuate within a certain range from the third day on, and declined sharply after about 10 days, nicotine concentration from 3rd to 10th day was fluctuate within 10-5-10-4mol/L.Postoperative wound healing, no significant difference in 3 days(P>0.05), after 7 days, the wound healing of experimental group significantly greater compared with the control (P=0.015).The wound was healed in 10 days after operative, there was no significant difference between two groups(P>0.05).The epithelial proliferation in the experimental group was significantly greater than that in the blank group, there were many fibroblasts, inflammatory cells and new capillaries, the epithelial process is short, the submucosa is loose, and a large number of collagen fibers are produced.The lamina propria is closely connected with the periosteum, and the wound is healed Conclusion Low concentration of nicotine sustained-release particles collagen membrane system may promote wound healing in the hard palate mucosa of rats.%目的 低浓度尼古丁可促进新生血管的形成,进而促进创伤愈合,文中旨在观察低浓度尼古丁胶原膜缓释微粒系统对大鼠硬腭黏膜创伤愈合的影响. 方法 以聚乳酸-羟基乙酸(PLGA)共聚物为载体材料,用复乳挥发法(w/o/w)制备低浓度尼古丁缓释微粒,以胶原膜为支架,制备低浓度尼古丁胶原膜缓释微粒系统.将Wistar大鼠48只分为实验组和空白组,每组24只,在硬腭前部造直径3mm的圆形创口,用6-0可吸收线分别将低浓度尼古丁胶原膜缓释微粒系统和空白胶原膜缝合于创口上,观察1、3、7、10d大鼠上腭组织创口愈合变化情况,并比较不同时间点愈合差异. 结果 电镜下尼古丁缓释微粒大体观呈现球形,大小均匀,球体表面粗糙,平均粒径(3.0±0.2)μm,其包封率和载药率分别为50.2%和4.12%.尼古丁缓释微粒第1天体外释放量较大,第2天释放量较小,从第3天尼古丁的释放量趋于稳定,且在一定的范围内波动,约在10d后急剧下降,在第3-10天尼古丁浓度为10-5-10-4mol/L波动.大体观术后3d时,2组创面愈合差异无统计学意义(P>0.05);术后7d时实验组的创口愈合面积大于空白组(P=0.015,);术后10d时,2组创面已基本愈合,差异无统计学意义(P>0.05).术后7d时,实验组上皮增生较空白组明显,且可见较多的成纤维细胞、炎症细胞及新生的毛细血管,上皮钉突较短,黏膜下层较疏松且新生大量的胶原纤维,固有层与骨膜紧密连接,创口基本愈合.空白组可见大量的炎性细胞,创口未完全愈合;术后10d时,2组创口上皮细胞增殖基本已完全完成,创口愈合. 结论 低浓度尼古丁胶原膜缓释微粒系统可能具有促进大鼠硬腭黏膜创伤愈合的作用.