齐墩果酸对氯化汞急性暴露致肝损伤的保护作用及可能机制  

Protective effect of oleanolic acid on liver injury induced by acute exposure to mercury chloride and its possible mechanism

作　　者：欧阳钏 马璇 赵佳丽 刘玉梅 柯鸿阳 李清华[1] 李晓红[1] 李万伟[1,2] OUYANG Chuan;MA Xuan;ZHAO Jiali;LIU Yumei;KE Hongyang;LI Qinghua;LI Xiaohong;LI Wanwei(School of Public Health,Weifang Medical University,Weifang,Shandong 261053,China;Weifang Key Laboratory of Health Inspection and Quarantine,Weifang,Shandong 261053,China)

机构地区：[1]潍坊医学院公共卫生学院,山东潍坊261053 [2]潍坊市卫生检验与检疫重点实验室,山东潍坊261053

出　　处：《环境与职业医学》2022年第11期1298-1303,共6页Journal of Environmental and Occupational Medicine

基　　金：山东省中医药卫生计划项目(2020M077);山东省医药卫生科技发展计划项目(2019WS592);山东省自然科学基金项目(ZR^(2)020MH336);中华医学会医学教育分会和中国高等教育学会医学教育专业委员会2020年医学教育研究立项课题项目(2020BN08142)。

摘　　要：[背景]氯化汞(HgCl_(2))急性暴露会导致肝损伤。齐墩果酸(OA)作为一种保肝药物,对HgCl_(2)急性暴露引起肝损伤的保护作用及相关机制尚不明确。[目的]探讨急性HgCl_(2)暴露导致小鼠肝损伤及OA的保护作用及可能机制。40只SPF级C57BL/6雄性小鼠,按照体重随机分为4组,每组10只。分别为对照组、OA组(300 mg·kg^(-1))、HgCl_(2)组(5 mg·kg^(-1))、OA+HgCl_(2)组(300 mg·kg^(-1)OA+5 mg·kg^(-1)HgCl_(2))。连续灌胃豆油、OA溶液两次,一天一次,于第2次灌胃2 h后,腹腔注射HgCl_(2)溶液,观察48 h后处死小鼠。收集小鼠血清和肝脏,计算肝脏系数,采用苏木素-伊红(HE)染色及普鲁士蓝染色观察肝脏结构变化及铁沉积状况。利用丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总超氧化物歧化酶(T-SOD)、还原型谷胱甘肽(GSH)、丙二醛(MDA)、组织铁含量试剂盒分别检测相应指标。采用Western blotting法检测小鼠肝脏核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、谷胱甘肽过氧化物酶4(Gpx4)、转铁蛋白受体1(TFR1)和溶质载体家族7成员11(SLC7A11)等蛋白的相对表达量。[结果]HgCl_(2)组小鼠AST、ALT水平分别为(76.447±9.695)U·g^(-1)、(98.563±24.673)U·g^(-1),均高于对照组(P<0.05)。OA预处理后,肝脏系数及上述指标分别降低至(4.769±0.237)%、(57.086±10.087)U·g^(-1)、(87.294±27.181)U·g^(-1),肝脏系数、AST水平与HgCl_(2)组相比,差异有统计学意义(P<0.05)。HgCl_(2)急性暴露后,小鼠肝细胞排列紊乱,并伴有炎性浸润,肝组织普鲁士蓝染色出现阳性蓝染颗粒;OA预处理后,肝组织上述变化得到改善。HgCl_(2)组肝组织铁含量为(3.646±0.238)μmol·g^(-1),高于对照组的(2.948±0.308)μmol·g^(-1);OA预处理后,铁含量降低至(3.429±0.415)μmol·g^(-1)。与对照组相比,HgCl_(2)急性暴露可导致肝组织GSH、T-SOD水平降低,Nrf2、HO-1、SLC7A11、Gpx4蛋白表达水平降低,MDA水平升高,TFR1蛋白表�[Background]Acute exposure to mercury chloride(HgCl_(2))can cause liver damage.Whether oleanolic acid(OA)as a hepatoprotective drug can protect against liver injury induced by acute exposure to HgCl_(2)and related mechanism of action remain unclear.[Objective]To investigate the protective effect and possible mechanism of OA on liver injury in mice caused by acute exposure to HgCl_(2).[Methods]Forty SPF C57 BL/6 male mice were randomly divided into four groups with 10 mice in each group according to body weight.The four groups were named control group,OA group(300 mg·kg^(-1)),HgCl_(2)group(5 mg·kg^(-1)),and OA+HgCl_(2)group(300 mg·kg^(-1)OA+5 mg·kg^(-1)Hgcl2).Soybean oil and OA solution were administered intragastric once a day for two consecutive days.HgCl_(2)solution was injected intraperitoneally 2 h after the second intragastric administration.Mice were sacrificed after 48 h,and their serum and liver were collected.Liver coefficient was calculated.The changes of liver structure and iron deposition were observed by hematoxylin-eosin(HE)staining and Prussian blue staining.Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total superoxide dismutase(T-SOD),reduced glutathione(GSH),malondialdehyde(MDA),and tissue iron content were measured with commercial kits.Western blotting was used to detect nuclear factor eryt h roid-2 related factor 2(N rf2),heme oxygenase 1(HO-1),glutathione peroxidase 4(Gpx4),transfe rrin receptor1(TFR1,)and solute carrier family 7 member 11(SLC7 A11).[Results]The AST and ALT levels of the HgCl_(2)group were(76.447±9.695)U·g^(-1)and(98.563±24.673)U·g^(-1),respectively,which were higher than those of the control group(P<0.05).After the OA pretreatment,the liver coefficient and the above indexes were decreased to(4.769±0.237)%,(57.086±10.087)U·g^(-1),and(87.294±27.181)U·g^(-1),respectively.The liver coefficient and AST level of the OA+HgCl_(2)group were significantly different from those of the HgCl_(2)group(P<0.05).After acute exposure to HgCl_(2),the hepatocytes of

关 键 词：齐墩果酸 氯化汞 肝损伤 氧化应激 

分 类 号：R114[医药卫生—卫生毒理学]