雌马酚对芥子气所致家兔皮肤损伤的治疗作用及其机制的初步研究

Therapeutic effect of equol on local skin wounds caused by mustard gas in rabbits and related mechanism

目的探讨具有雌激素样活性的雌马酚(equol,Eq)对芥子气染毒皮肤创面愈合的影响及可能的机制。方法以芥子气(0.5 mg/cm2)染毒家兔臀部皮肤为实验模型,染毒创面连续1周外用不同浓度(10、50、100μmol/L)的Eq后,观察创面外观变化;取创面活检标本观察组织病理学变化;用流式细胞术分析细胞凋亡、DNA周期变化;用试剂盒检测染毒创面中IL-6、TNF-α的浓度。结果染毒120 h后,所有治疗组染毒创面红斑、水肿、糜烂、坏死等皮损评分低于染毒对照组(P<0.05);染毒168 h后,50μmol/L治疗组染毒创面组织病理学炎症、坏死等改变评分低于染毒对照组(P<0.05),各治疗组细胞凋亡百分比低于染毒对照组(P<0.05),各治疗组细胞DNA(S+G2-M)周期百分比高于染毒对照组(P<0.05),治疗组细胞中的IL-6、TNF-α含量低于染毒对照组(P<0.05)。结论 Eq可能通过抑制皮损局部炎症反应减少细胞凋亡,增强细胞增殖能力,从而促进芥子气所致皮肤损伤的愈合。

Objective To study the therapeutic effect of estrogenic equol（Eq） on mustard gas-caused skin wounds and the possible mechanism.Methods A rabbit skin wound model was established by contaminating the hip skin with mustard gas（0.5 mg/cm 2）.The contaminated wound was treated externally with different concentrations（10,50,and 100 μmol/L） of Eq for a week,and the changes of the wound were observed macroscopically.Wound specimens were collected for histopathological evaluation.Cell apoptosis and DNA cycle changes were analyzed by flow cytometry.Levels of IL-6 and TNF-α in the contaminated wound specimens were detected.Results The scores of erythema,edema,erosion and necrosis of the contaminated wounds in the treatment groups were significantly lower than those in the control group 120 h after mustard gas exposure（P〈0.05）.The scores for changes of histopathological inflammation and necrosis were significantly lower in the 50 μmol/L Eq treatment group than those in the control group 168 h after mustard gas exposure（P〈0.05）.The results of flow cytometry showed that the proportion of apoptotic cells in the control group was significantly higher than those in the treatment groups 168 h after mustard gas exposure（P〈0.05）,and the proportion of cells in DNA（S ＋ G 2-M） phase in the treatment groups was significantly higher than that in the control group（P〈0.05）.The levels of IL-6 and TNF-α in the treatment groups were significantly lower than those in the control group 168 h after mustard gas exposure （P 〈0.05）.Conclusion Eq can promote healing of mustard gas-caused local skin damaged by inhibiting inflammatory response and cell apoptosis and enhancing cell proliferation.