人重组表皮生长因子促进鼓膜创伤愈合的动物实验研究

Acceleration of Wounded Healing with Topical Application of Recombinant Human Epidermal Growth Factor in Guinea Pigs' Tympanic Membranes

目的探讨局部应用人重组表皮生长因子(rhEGF)对鼓膜创伤愈合的作用和组织愈合特点。方法建立豚鼠的鼓膜穿孔模型,第一组10只豚鼠,鼓膜穿孔为1mm×1mm大小,左、右耳局部分别滴注rhEGF、生理盐水,观察有否合并中耳感染及其程度;第二组30只豚鼠,鼓膜的穿孔为2mm×2mm大小,其中20只豚鼠左右耳局部分别滴注rhEGF、生理盐水,10只为空白对照,并进行预防性抗感染处理,在不同时期用电耳镜、光镜及透射电镜对创面的愈合速度及鼓膜形态学的变化进行观察。结果第一组10只豚鼠中,左、右耳出现化脓性中耳炎的分别是6和7耳,无感染耳的鼓膜均愈合;第二组30只豚鼠中,局部滴注rhEGF20耳的平均愈合时间为8.5±3.0d,局部滴注生理盐水的20耳为11.8±2.6d,空白对照组20耳为12.8±2.3d,局部滴注rhEGF的鼓膜创伤愈合速度明显快于滴注生理盐水及空白对照的创伤鼓膜(P<0.05)。滴注rhEGF的鼓膜在创伤后2周时外层的鳞状上皮已增生覆盖创面,内层的扁平上皮增生,两层上皮间未见明显结构组织;滴注生理盐水的鼓膜在创伤后2周时创面见少量鳞状上皮及肉芽疤痕组织。结论rhEGF能促进创伤鼓膜的组织恢复,且rhEGF局部应用于创伤鼓膜后,在短期内不会引起组织钙化、疤痕增生。

Objective To explore the function and characteristic of recombinant human epidermal growth factor （rhEGF） in the treatment of perforated tympanic membrane in guinea pigs. Methods The wounded model was designed in 40 guinea pigs ear drums. The wound of tympanic membranes were 1 mm × 1 mm and 2 mm × 2 mm in the first and second group respectirely. The guinea pigs of second group were injected antibiotic for two weeks. It was observed that the healing speed and the morphological changes of the wounded tympanic membranes of guinea pigs with topical application of rhEGF, physiological saline and blank by otologyscope, microscope and electron microscope. Results In the first group, there were six eats developed suppurative otitis in the guinea pigs with application of rhEGF and seven ears in the guinea gigs with physiological saline. In the second group, the average healing time of tympanic membranes in the guinea pigs receiving rhEGF was 8.5 ± 3.0 days, that with physiological saline was 11.8 ± 2.6 days,that with blank contrast was 12.8 ± 2.3 days. Compared with groups of physiological saline and blank contrast, the healing time of the guinea pigs with rhEGF was faster.There was significant difference （ P 〈 0.05）. In the healing tympanic membranes with rhEGF, the wounded area was covered completely by outer squamous epithelium, the lining flat epithelium of ear drum was regenerated. However, in the healing tympanic membrane with physiological saline, there was little squamous epithelium in the wounded area, more granulation and scar tissue could be seen. Conclusion Recombinant human epidermal growth factor can accelerate the wounded healing in guinea pig tympanic membranes. RhEGF does not cause the tissue calcify, scar formation in the short time, but maybe increase the opportunity of infection.