曲古抑菌素抑制增生性瘢痕形成的实验研究

The experimental study on trichostatin a in inhibiting hypertrophic scar

目的探讨曲古抑菌素(Trichostatin A,TSA)对兔耳增生性瘢痕的作用及对成纤维细胞周期和凋亡的影响。方法建立兔耳腹侧面瘢痕增生模型,一侧兔耳注射TSA(1.0μmol/L),另一侧注射生理盐水作为自身对照。观察不同时间瘢痕外形变化,组织学变化,检测bcl-2的含量的变化,分析各时间点瘢痕组织内细胞周期及细胞凋亡率的变化。结果随着药物作用时间延长,TSA组与对照组相比①瘢痕增生块厚度明显减小(P<0.05),质地变软。②镜下观察见成纤维细胞数目减少,bcl-2阳性细胞逐渐增多,30天时两组bcl-2阳性细胞所占比率都超过50%。③处在S期的细胞所占比例逐渐减少,细胞被抑制在G1/G2期,与对照组相比变化显著(P<0.05)。④凋亡细胞百分率则呈下降趋势,早期时明显高于对照组,30天时两组比较无明显差别。结论兔耳早期增生性瘢痕局部注射曲古抑菌素可抑制瘢痕增殖过程,使瘢痕纤维化程度减轻。

Objective To study the effect of Trichostatin A（TSA） on the hypertrophic scar of rabbit ears and on the cell cycle and cell apoptosis of fibroblasts. Methods The model of dermal hypertrophic scar in the 18 rabbits＇ears was established. One ear dermal hypertrophic scar of each rabbit was treated by TSA （1.0μmol/L）, the another was treated by normal saline. The effect of TSA on scar was checked by observing the changes in outline form and thickness of rabbit ear scars. The changes of histology under microscope, changes of bcl-2 expression, cell cycle and apoptosis rate were checked simultaneously.Results Compared with the control group, as time increased in TSA group：① thickness of rabbit ear scars grew down greatly（P〈0.05） and texture became soft. ②Number of fibroblasts reduced and cell of bcl-2（＋） gradually increased. Bcl-2（＋） cells rate exceed 50% of all groups,after 30 days. ③S-phase cells rate gradually reduced,and cells were restrained G1/G2 phase. TSA group had a greatly chang compared with the control group（P〈0.05）. ④Apoptosis cell rate showed downtrend, obviously exceeded normal saline group in early.There were no obviously differents between TSA group and normal saline group.Conclusion TSA could induce scar degradation in the model of dermal hypertrophic scar in the rabbit ear and may reduce the fibrosis level.