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白藜芦醇和bFGF联合治疗芥子气所致家兔皮肤损伤的初步研究
梁晓博1,刘继勇2,吴建华3*
0
(1. 解放军第309医院皮肤科, 北京 100091;
2. 第二军医大学长海医院药材科, 上海 200433;
3. 第二军医大学长海医院皮肤科, 上海 200433*通信作者)
摘要:
目的 探讨不同比例的白藜芦醇和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)联合药物凝胶制剂对芥子气染毒皮肤创面的治疗效果,为优化联合药物凝胶制备比例提供实验参考数据。方法 以芥子气(1.0 mg/cm2)染毒家兔背部皮肤为实验模型,设置治疗组1~11、阳性治疗对照组和染毒阴性对照组,每组3只染毒模型动物。将白藜芦醇(0.01、0.02、0.04 g/mL 3个浓度)与bFGF(0.42、2.08、4.17 μg/mL)3个浓度)以不同比例配制成联合药物凝胶制剂。治疗组1~11染毒创面连续14 d外用不同成分比例的联合药物,阳性治疗对照组和染毒阴性对照组分别用醋酸去炎松霜和不含任何药物的凝胶作相同处理,观察创面外观变化,按照既定标准对创面损伤程度进行打分;并取创面活检标本,进行H-E染色,观察组织病理学变化,综合评价各种联合药物促进创面愈合的能力。结果 外用不同联合药物3 d后,治疗组5染毒创面红斑、糜烂、坏死等皮肤损伤评分和组织病理学炎症、坏死等改变评分明显低于染毒阴性对照组和其他联合药物治疗组(P<0.05),与阳性治疗对照组比较,差异无统计学意义(P>0.05)。结论 治疗组5使用的联合药物凝胶(0.02 g/mL白藜芦醇+2.08 μg/mL bFGF)通过抑制皮损局部炎症反应,减少细胞坏死,能够有效促进芥子气所致皮肤损伤的愈合。
关键词:  芥子气  中毒  皮肤损伤  白藜芦醇  成纤维细胞生长因子2
DOI:10.3724/SP.J.1008.2014.00957
投稿时间:2014-03-25修订日期:2014-06-19
基金项目:国家重大新药创制专项基金项目(2011ZXJ09102-02B),长海医院“1255”学科建设计划项目(CH125531800).
Resveratrol combined with bFGF for treatment of mustard gas-induced skin wound in rabbits
LIANG Xiao-bo1,LIU Ji-yong2,WU Jian-hua3*
(1. Department of Dermatology, No. 309 Hospital of PLA, Beijing 100091, China;
2. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
3. Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
* Corresponding author.)
Abstract:
Objective To study the wound-healing effect of combined gel preparation of different proportions of resveratrol and basic fibroblast growth factor(bFGF)on mustard gas-contaminated wounds, so as to provide evidence for optimizing the preparation of the combined drug gel. Methods A wound model was established by contaminating the back skin of rabbits with mustard gas (1.0 mg/cm2). The study was divided into treatment groups 1-11, positive treatment group, and negative contamination group, with 3 model animals in each group. The resveratrol (0.01, 0.02, and 0.04 g/mL) and bFGF (0.42, 2.08, and 4.17 μg/mL) were used to prepare combined drug gel by different proportions. The treatment groups 1-11 were treated externally with combined drug gels of corresponding proportions for 14 days. The positive treatment group and negative contamination group were treated with triamcinolone acetonide cream and gel without drugs, respectively. Changes of the wound appearance were observed and the healing extents were graded by predefined standard. Wound specimens were also collected for histopathological evaluation using H-E staining. The effects of different drug gel preparations on mustard gas-contaminated wounds were evaluated comprehensively. Results After external use of the combined drug gels for 3 d, the scores of skin injury including erythema, erosion and necrosis, histopathological inflammation, and necrosis of the contaminated wounds in treatment group-5 were significantly improved compared with those in the negative contamination group and other combined drug treatment groups(P<0.05), while showed no significant differences with the positive treatment group (P>0.05). Conclusion Combined drug gels in treatment group-5(0.02 g/mL resveratrol+2.08 μg/mL bFGF)can promote healing of the skin wound caused by mustard gas through inhibiting inflammatory response and cell necrosis of the wounded skin.
Key words:  mustard gas  poisoning  skin wounds  resveratrol  fibroblast growth factor 2