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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
郑庆虎1,于蕊2,刘强1,赵静1,徐立3,周欣1,孙本全1,高莉4,梁晓博5*,吴建华1*
0
(1. 第二军医大学长海医院皮肤科,上海 200433
2. 解放军71320部队门诊部皮肤科,开封 475003
3. 第二军医大学长海医院急诊科,上海 200433
4. 第二军医大学长海医院病理科,上海 200433
5. 解放军309医院皮肤科,北京 100091
*通信作者)
摘要:
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、100 μmol/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,50 μmol/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。
关键词:  芥子气  中毒  接触性皮炎  雌马酚
DOI:10.3724/SP.J.1008.2012.00818
投稿时间:2012-04-15修订日期:2012-06-28
基金项目:国家科技部重大专项 (2009ZXJ09004-075, 2011ZXJ09102-02B), 第二军医大学长海医院“1255计划”项目.
Therapeutic effect of equol on local skin wounds caused by mustard gas in rabbits and related mechanism
ZHENG Qing-hu1,YU Rui2,LIU Qiang1,ZHAO Jing1,XU Li3,ZHOU Xin1,SUN Ben-quan1,GAO Li4,LIANG Xiao-bo5*,WU Jian-hua1*
(1. Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Dermatology, No.71320 Troop of PLA, Kaifeng 475003, Henan, China
3. Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
4. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
5. Department of Dermatology, No. 309 Hospital of PLA, Beijing 100091, China
*Corresponding authors.)
Abstract:
ObjectiveTo study the therapeutic effect of estrogenic equol (Eq) on mustard gas-caused skin wounds and the possible mechanism. MethodsA rabbit skin wound model was established by contaminating the hip skin with mustard gas (0.5 mg/cm2). 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. ResultsThe 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+G2-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). ConclusionEq can promote healing of mustard gas-caused local skin damaged by inhibiting inflammatory response and cell apoptosis and enhancing cell proliferation.
Key words:  mustard gas  poisoning  contact dermatitis  equol