马来酸噻吗洛尔滴眼液对兔耳增生性瘢痕组织形成的影响

Effect of topical timolol maleate on hypertrophic scar formation in rabbit ears

目的观察马来酸噻吗洛尔滴眼液(topical timolol maleate,TTM)对兔耳增生性瘢痕模型形态学与组织学的影响。方法选取日本大耳白兔12只,在双侧耳腹侧分别制作4个直径为1 cm的圆形切口,术后21 d上皮化完成之日起随机将其分为3组,分别为模型组(不予任何处理)、生理盐水组(每日外敷生理盐水1 ml,每日2次,每次1 h)、TTM组(每日外敷马来酸噻吗洛尔滴眼液1 ml,每日2次,每次1 h),每组32个瘢痕模型。术后49 d给予标本取材,苏木精-伊红(HE)染色后观察瘢痕增生指数及组织病理学变化;免疫组化检测血管内皮生长因子(VEGF)、CD34的表达情况,测量微血管密度。结果给予不同方式处理后,模型组与生理盐水组创面瘢痕增生率高于TTM组。用药治疗4周后,TTM组瘢痕颜色较模型组与生理盐水组明显变淡,成纤维/肌成纤维细胞数量较少,新生血管及炎性细胞浸润较轻,胶原纤维疏松、排列较规律,且温哥华瘢痕量表(VSS)评分、瘢痕增生指数、VEGF表达量、微血管密度均低于模型组与生理盐水组(P<0.05)。结论马来酸噻吗洛尔滴眼液可以通过减少VEGF分泌及微血管形成的数量,抑制兔耳增生性瘢痕组织中成纤维/肌成纤维细胞过度增生以及胶原纤维的过度沉积,改善胶原纤维的密度、形态、排列,进而减轻兔耳增生性瘢痕的严重程度。

Objective To observe the effect of topical timolol maleate(TTM)on the morphology and histology of rabbit ear hypertrophic scar model.Methods 12 Japanese white rabbits were selected.Four circular incisions with a diameter of 1 cm were made on the ventral sides of both ears.They were randomly divided into three groups from the date of completion of dermatization 21 days after operation.They were respectively model group(without any treatment),normal saline group(1 ml of normal saline was applied externally every day,twice a day,1 hour each time),TTM group(topical timolol maleate eye drops 1 ml daily,twice a day,1 hour each time),32 scar models in each group.The specimens were taken 49 days after operation,and the scar hyperplasia index and histological changes were observed after he staining;The expressions of vascular endothelial growth factor(VEGF)and CD34 were measured by immunohistochemistry,and the microvessel density was measured.Results After different treatments,the rate of wound scar hyperplasia in model group and normal saline group was higher than that in TTM group.After 4 weeks of treatment,the scar color in TTM group was significantly lighter than that in model group and normal saline group,the number of fibroblasts/myofibroblasts was less,the infiltration of neovascularization and inflammatory cells was less,the collagen fibers were loose and arranged regularly,and the vancouver scar scale(VSS)score,scar hyperplasia index,VEGF expression and microvessel density in TTM group were lower than those in model group and normal saline group.Conclusion TTM can inhibit the excessive proliferation of fibroblasts/myofibroblasts and the excessive deposition of collagen fibers in rabbit ear hypertrophic scar tissue by reducing the secretion of vascular endothelial growth factor and the number of microvessels,improve the density,shape and arrangement of collagen fibers,and then reduce the severity of rabbit ear hypertrophic scar.