摘要
目的探讨线粒体抗氧化剂甲磺酸米托醌(MitoQ)对氮芥(HN2)诱导小鼠急性肝损伤(ALI)的保护作用及相关机制。方法将40只雄性C57BL/6小鼠随机分为4组:对照组、MitoQ对照组、HN2染毒组、MitoQ+HN2组(MitoQ治疗组)。检测指标如下:体质量;血清谷丙转氨酶(ALT)和谷草转氨酶(AST)活性;肝组织Bcl-2、Bax蛋白表达、caspase-3活性、凋亡细胞比例;肝组织HE染色检测病理结构变化;血清血糖水平、血清和肝组织三酰甘油(TG)水平;油红O染色检测肝中性脂肪含量;肝组织丙二醛(MDA)含量、还原型谷胱甘肽和活性氧(ROS)水平;血清炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)浓度。结果2 mg/kg的HN2腹腔染毒可以成功诱导小鼠发生ALI,同时伴有糖脂代谢紊乱。与HN2染毒组小鼠相比,MitoQ治疗组小鼠血清ALT和AST活性降低(P<0.05),肝病理损伤程度显著减轻,Bax/Bcl-2比值、caspase-3活性和凋亡细胞比例降低(P<0.05),肝组织TG含量明显升高(P<0.05),同时肝组织MDA含量和ROS水平显著降低(P<0.05)。此外,MitoQ干预后小鼠血清TNF-α和IL-6浓度较HN2染毒组显著降低(P<0.05)。结论MitoQ通过抗凋亡、抗氧化和抗炎作用发挥拮抗HN2诱导小鼠ALI的作用,可能是HN2中毒的潜在候选药物。该研究为糜烂性毒剂中毒的临床救治提供了新思路。
Objective To investigate the protective effect and related mechanism of mitochondrial antioxidant mitoquinone mesylate(MitoQ)on nitrogen mustard(HN2)-induced acute liver injury(ALI)in mice.Methods Forty male C57BL/6 mice were randomly divided into four groups:control group,MitoQ control group,HN2 exposure group,and MitoQ+HN2 group(MitoQ treatment group).The following indicators were detected:body mass,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities;Bcl-2 and Bax protein expression,caspase-3 activity,and proportion of apoptotic cells in liver tissues;pathological structural changes detected by HE staining in liver tissues;serum blood glucose level,triglyceride(TG)level in serum and liver tissues;neutral fat content in liver detected by oil red O staining;malondialdehyde(MDA)content in liver tissues,reduced glutathione and reactive oxygen species(ROS)levels;and concentrations of serum inflammatory factors such as TNF-αand IL-6.Results Intraperitoneal administration of 2 mg/kg HN2 could successfully induce ALI in mice,accompanied by glucose and lipid metabolism disorders.Compared with mice in HN2 exposure group,the serum ALT and AST activities were decreased(P<0.05),the degree of liver pathological damage was significantly alleviated,Bax/Bcl-2 ratio,caspase-3 activity and proportion of apoptotic cells were decreased(P<0.05),the content of TG in liver tissues was significantly increased(P<0.05),while the levels of MDA and ROS in liver tissues were significantly reduced(P<0.05)in MitoQ treatment group.In addition,the concentrations of serum TNF-αand IL-6 in mice with MitoQ intervention were significantly lower than those in HN2 exposure group.Conclusion MitoQ plays an antagonistic role against HN2-induced ALI in mice through anti-apoptosis,antioxidation and anti-inflammatory effects,and may be a potential drug candidate for HN2 poisoning.This study provides new ideas for the clinical treatment of blister agent poisoning.
作者
刘江正
宋德心
马丞飞
刘思佳
赵昱舜
刘建豪
徐安琦
艾多
龙子
孔德钦
海春旭
LIU Jiangzheng;SONG Dexin;MA Chengfei;LIU Sijia;ZHAO Yushun;LIU Jianhao;XU Anqi;AI Duo;LONG Zi;KONG Deqin;HAI Chunxu(Department of Military Toxicology and Chemical Defense Medicine,Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine,Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment,School of Military Preventive Medicine,2 No.4 Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China)
出处
《空军军医大学学报》
CAS
2023年第3期222-228,共7页
Journal of Air Force Medical University
基金
国家自然科学基金(31900892)。
关键词
氮芥
肝损伤
线粒体抗氧化剂
甲磺酸米托醌
nitrogen mustard
liver injury
mitochondrial antioxidant
mitoquinone mesylate
作者简介
刘江正,博士,讲师,从事化学战剂损伤与防治研究,Tel:18829256166,E-mail:liujiangzh@fmmu.edu.cn;通信作者:海春旭,Tel:13609198968,E-mail:cx-hai@fmmu.edu.cn;通信作者:孔德钦,Tel:13571975268,E-mail:1084789645@qq.com。
