摘要
目的探讨红系衍生的核因子2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf-2)激动剂特丁基对苯二酚(tert-butylhydroquinone,tBHQ)对氮芥(nitrogen mustard,HN2)诱导急性肝损伤的保护作用及其机制。方法给予C57BL/6小鼠腹腔单次注射盐酸HN2(2 mg/kg)构建HN2诱导急性肝损伤模型,染毒前0.5 h、染毒后1h和6h分别给予tBHQ(20 mg/kg)进行干预,HN2染毒3天后处死小鼠并取材检测,进而探讨tBHQ对HN2诱导的小鼠急性肝损伤是否具有保护作用并研究其保护机制。检测指标如下:肝组织大体改变和苏木精-伊红(hematoxylin-eosin,HE)染色病理变化;血清谷氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性;肝组织活性氧(reactive oxygen species,ROS)水平,丙二醛(malondialdehyde,MDA)含量,还原型谷胱甘肽(reduced glutathione,GSH)含量;肝组织髓过氧化物酶(myeloperoxidase,MPO)活性,血清炎症因子肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白细胞介素6(interleukin 6,IL-6)含量;肝组织氧化还原调控分子Nrf-2的mRNA和蛋白表达水平。结果2 mg/kg的HN2单次腹腔暴露可以成功诱导小鼠肝组织氧化损伤和炎症反应。与HN2染毒组小鼠相比,tBHQ干预显著减轻小鼠肝组织病理损伤程度,血清ALT和AST活性降低(P均<0.05)。同时tBHQ显著抑制了HN2染毒导致的肝组织ROS水平和MDA含量升高及GSH含量降低(P均<0.05)。此外,HN2+tBHQ治疗组小鼠的肝组织MPO活性及血清TNF-α、IL-6含量较HN2染毒组均显著降低(P均<0.05)。最后,tBHQ干预上调了HN2染毒后Nrf-2的mRNA和蛋白表达水平(P均<0.05)。结论tBHQ通过激活Nrf-2发挥抗氧化和抗炎作用,能够有效减轻HN2染毒诱导的急性肝损伤,tBHQ可能是一种HN2中毒临床救治的有效候选药物。
Objective To investigate the protective effects and machanisms of erythroid-derived nuclear factor erythroid 2-related factor 2(Nrf-2) agonist tert-butylhydroquinone(tBHQ) against nitrogen mustard(HN2) induced acute liver injury.Methods C57 BL/6 mice were given a single intraperitoneal injection of hydrochloride HN2(2 mg/kg) to establish the HN2-induced acute liver injury model, and these mice were given tBHQ(20 mg/kg) for intervention 0.5 h before, 1 h and 6 h after exposure of HN2, mice were sacrificed 3 days after exposure to HN2 and the samples were collected for detection, and then to explore whether tBHQ had a protective effect on HN2-induced acute liver injury in mice and to study its protective mechanisms. The following indicators were detected: general changes in liver tissue and pathological changes by hematoxylin-eosin(HE) staining;serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activities;reactive oxygen species(ROS) level of liver tissue, malondialdehyde(MDA) content, reduced glutathione(GSH) content;myeloperoxidase(MPO) activities of liver tissue, serum inflammatory factor of tumor necrosis factor alpha(TNF-α) and interleukin 6(IL-6) content;mRNA and protein expression levels of redox regulatory molecule Nrf-2 in liver tissue.Results A single intraperitoneal exposure of 2 mg/kg HN2 could successfully induce oxidative damage and inflammatory response in liver tissue in mice. Compared with HN2-exposed mice, tBHQ intervention significantly reduced the degree of pathological damage in the liver tissue of mice, and decreased the activities of serum ALT and AST(all P<0.05). At the same time, tBHQ treatment significantly inhibited the increase of ROS level and MDA content and the decrease of GSH content in liver tissue caused by HN2 exposure(all P<0.05). In addition, the MPO activities in liver tissue and the contents of serum TNF-α and IL-6 in the HN2+tBHQ treatment group were significantly lower than those in the HN2 exposure group(all P<0.05). Finally, tBHQ intervention up-regu
作者
徐安琦
艾多
马丞飞
刘建豪
刘思佳
赵昱舜
孔德钦
刘颖
龙子
刘江正
XU Anqi;AI Duo;MA Chengfei;LIU Jianhao;LIU Sijia;ZHAO Yushun;KONG Deqin;LIU Ying;LONG Zi;LIU Jiangzheng(School of Basic Medicine,Air Force Medical University,Xi'an Shaanxi 710032,China)
出处
《华南国防医学杂志》
CAS
2022年第11期845-852,共8页
Military Medical Journal of South China
基金
国家自然科学基金青年基金资助项目(31900892)。
关键词
特丁基对苯二酚
氮芥
肝损伤
氧化应激
炎症
保护作用
Tert-butylhydroquinone
Nitrogen mustard
Liver injury
Oxidative stress
Inflammation
Protective effect
