可视化血红素加氧酶-1小鼠模型用于药物肝毒性评价  

Dynamic imaging of heme oxygenase 1 expression in mouse livers for drug-hepatotoxicity evaluation

作　　者：刘磊 张玉龙 王小慧 詹林盛 LIU Lei;ZHANG Yu-long;WANG Xiao-hui;ZHAN Lin-sheng(Institute of Health Service and Transfusion Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院卫生勤务与血液研究所,北京100850

出　　处：《军事医学》2021年第7期510-515,共6页Military Medical Sciences

基　　金：国家自然科学基金青年科学基金项目(81800183)。

摘　　要：目的建立实时动态监测药物肝毒性小鼠模型,用于药物肝毒性临床前评价。方法通过水动力高压转染法将表达萤火虫荧光素酶的血红素加氧酶-1(HO-1)报告基因质粒转染到小鼠肝细胞中,建立HO-1-Luc小鼠模型。使用HO-1-Luc小鼠模型动态监测对乙酰氨基酚(APAP)导致的肝损伤以及抗氧化剂谷胱甘肽对药物性肝损伤的治疗效果。结果使用HO-1-Luc小鼠模型通过活体荧光成像的手段能监测到APAP引起的肝毒性,与通过活性氧相关标志物、转氨酶以及组织病理学等经典肝毒性检测手段得到的结果吻合。同时该小鼠模型能够监测到谷胱甘肽对APAP诱导的肝毒性保护作用。结论建立的HO-1-Luc小鼠模型在药物临床前肝毒性评价中具有潜在应用价值。Objective To establish a mouse model that is capable of dynamic monitoring of drug hepatotoxicity for preclinical evaluation.Methods The reporter gene plasmid of heme oxygenase 1(HO-1)expressing firefly luciferase was transfered into hepatocytes by hydrodynamic gene delivery.HO-1-Luc mice were used to monitor the hepatotoxicity caused by the tool drug,acetaminophen(APAP),dynamically and the therapeutic effect of the antioxidant glutathione against APAP-induced hepatotoxicity.Results Hepatotoxicity induced by APAP could be monitored with HO-1-Luc mice using bioluminescence imaging,which was consistent with the hepatotoxicity results obtained with classical methods,including the detection of reactive oxygen-related markers,transaminase and hepatic histopathology.Furthermore,the therapeutic effect of glutathione against APAP-induced hepatotoxicity could be monitored by the HO-1-Luc mice.Conclusion These results indicate that the HO-1-Luc mouse model can be potentially used in preclinical hepatotoxicity risk assessment.

关 键 词：活体荧光成像 水动力高压转染 血红素加氧酶-1 自由基 药物肝毒性 

分 类 号：H965[语言文字]