BALB/c小鼠硫芥类化合物皮肤染毒模型的构建及洗消  

Construction of sulfur mustard analogue-induced skin contamina⁃tion models in BALB/c mice and its decontamination

作　　者：郭帅 邢欢纯 曹文斌 王淋 陈爱兵[1] 王永安 杨军 GUO Shuai;XING Huanchun;CAO Wenbin;WANG Lin;CHEN Aibing;WANG Yongan;YANG Jun(School of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China;Academy of Military Medical Sciences,Beijing 100850,China;Tianjin University of Science and Technology,Tianjin 300222,China)

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]军事医学研究院,北京100850 [3]天津科技大学生物工程学院,天津300222

出　　处：《中国药理学与毒理学杂志》2025年第4期277-284,共8页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的构建硫芥类似物1-氯-2-乙基硫基乙烷(CEES)诱导不同品系小鼠皮肤染毒模型,并评估反应性皮肤去污乳液合剂(RSDL)的洗消效果。方法(1)以昆明小鼠、BALB/c小鼠、BALB/c-nu小鼠和C57BL/6N小鼠为实验动物,以暴露染毒与覆膜染毒2种给药方式对小鼠背部皮肤(4 cm2)实施CEES染毒(75μL·kg^(-1),暴露10 min),通过创面愈合天数和面积确定建模品系和染毒方法;(2)对建模动物采用覆膜染毒法实施CEES浓度梯度(75、150、250、350和500μL·kg^(-1),暴露10 min)染毒,通过创面愈合天数和面积,结合Kaplan-Meier生存曲线,确定最佳染毒剂量;(3)对建模动物用覆膜染毒法进行背部CEES染毒(固定剂量150μL·kg^(-1),暴露时间分别为5、10和20 min),通过创面愈合天数和面积,结合Kaplan-Meier生存曲线,确定最佳染毒时间。(4)将建模动物分为染毒对照组(CEES剂量覆膜染毒10 min)、洗消组(覆膜染毒10 min后RSDL洗消)、5 min洗消组(覆膜染毒5 min后给予RSDL洗消,再覆盖保鲜膜5 min)和即时洗消组(给予CEES后,立即RSDL洗消,再覆盖保鲜膜10 min)通过创面面积、皮下微泡的数量和角质层厚度以及炎症因子白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)蛋白表达水平评估建模动物RSDL洗消效果。结果(1)相较于暴露染毒法,覆膜染毒法创面面积更大,创面愈合更缓慢;4种品系小鼠CEES染毒后,BALB/c小鼠创面面积最大,创面愈合最缓慢,确定BALB/c小鼠为建模动物。(2)CEES(250、350和500μL·kg^(-1))染毒后BALB/c小鼠存活率均<50%,CEES 150μL·kg^(-1)染毒后BALB/c小鼠存活率为83.3%,确定CEES 150μL·kg^(-1)为最佳染毒剂量;(3)CEES 150μL·kg^(-1)染毒20 min组小鼠3 d内全部死亡,染毒5 min组小鼠创面面积在相同时间均<染毒10 min组,确定10 min为最佳染毒时间;(4)在洗消组与染毒对照组中,CEES诱导的皮肤损伤可导致表皮细胞核固缩、毛囊结构破坏、炎症细胞浸润及皮下微泡形成。相较于OBJECTIVE To establish skin contamination models with sulfur mustard analogue 1-chloro-2-ethylsulfanyl ethane(CEES),and evaluate the therapeutic efficacy of reactive skin decontamination lotion kit(RSDL).METHODS①Kunming,BALB/c,BALB/c-nu,and C57BL/6N were contaminted with CEES 75μL·kg^(-1) using exposed method and covered method for 10 min on the dorsal skin.Wound healing times and areas were assessed to determine the stock of mice and exposure method.②BALB/c mice were exposed to a gradient of CEES at the doses of 75,150,250,350 and 500μL·kg^(-1)(10 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were used to determine the optimal dose.③BALB/c mice were exposed to CEES 150μL·kg^(-1) for varying durations(5,10 and 20 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were analyzed to determine the optimal exposure time.④BALB/c mice were divided into four groups:control(exposed with the covered method at 150μL·kg^(-1),10 min),treatment(20μL RSDL treatment after exposure,as the control group),5 min treatment(20μL RSDL treatment after 5 min of exposure,followed by 5 min of coverage)and immediate-treatment(exposed with the exposed method at 150μL·kg^(-1),immediately treated with 20μL RSDL,followed by 10 min of coverage).The therapeutic efficacy was evaluated based on the wound area,subcutaneous microvesicle count,epidermal thick⁃ness,and inflammatory cytokine(IL-6 and TNF-α)expressions.RESULTS①The covered method caused more severe and prolonged wounds than the exposed method.BALB/c mice exhibited a high sensitivity to CEES with delayed wound healing and were therefore selected as the model animal.②Survival rates in BALB/c mice dropped below 50%at doses of 250,350 and 500μL·kg^(-1),whereas an 83.3%survival rate was observed at 150μL·kg^(-1).③The mice exposed to CEES(150μL·kg^(-1),20 min)died within 3 days.The wound area was consistently smaller in the 5 min covered group than in the 10 min covered group.④CE

关 键 词：芥子气 皮肤损伤 动物模型 

分 类 号：R99[医药卫生—毒理学] R965[医药卫生—药学]