巴豆醛亚慢性染毒致雄性大鼠肝脏氧化损伤与炎性作用  

Liver inflammation and oxidative damage induced by subchronic crotonaldehyde exposure in male rats

作　　者：张淑曼 张琦 张彪 张志虎[1] ZHANG Shuman;ZHANG Qi;ZHANG Biao;ZHANG Zhihu(Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Ji'nan,Shandong 250062,China)

机构地区：[1]山东省职业卫生与职业病防治研究院山东第一医科大学(山东省医学科学院),山东济南250062

出　　处：《中国职业医学》2020年第4期396-401,共6页China Occupational Medicine

基　　金：山东省重点研发计划(2019GSF111069)。

摘　　要：目的探讨巴豆醛亚慢性染毒致雄性大鼠肝脏毒性作用,分析其可能的作用机制。方法将无特定病原体级雄性Wistar大鼠随机分为对照组和低、中、高剂量组,每组10只;分别予剂量为0.0、2.5、4.5、8.5 mg/kg体质量的巴豆醛溶液灌胃染毒,每天1次,每周5 d,连续染毒90 d。染毒期间称量大鼠体质量;染毒结束后,观察大鼠肝脏脏器系数和组织病理学改变,采用比色法检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活力和总胆红素(TBIL)水平,采用比色法检测肝组织中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平和还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)活力,采用酶联免疫吸附实验法测定肝组织中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)和γ干扰素(IFN-γ)水平。结果染毒结束后,3个剂量组大鼠体质量增加量均低于对照组(P<0.05);中、高剂量组大鼠肝脏脏器系数均低于对照组(P<0.05);3个剂量组大鼠肝组织均出现不同程度的炎性细胞浸润。大鼠血清中ALT、AST活力和TBIL水平均随着巴豆醛染毒水平升高而升高(P<0.01)。随着巴豆醛染毒剂量的升高,大鼠肝组织中MDA水平升高(P<0.01),GSH水平和GSH-Px、SOD活力均下降(P<0.01),IL-1β、IL-6、TNF-α和IFN-γ水平均升高(P<0.05)。结论巴豆醛暴露可致大鼠肝组织损伤;其机制可能与氧化平衡状态改变及上调肝组织炎性因子表达等作用有关,并呈一定程度的剂量-效应关系。Objective To investigate the hepatotoxicity induced by subchronic crotonaldehyde exposure in male rats and analyze its possible mechanism.Methods The specific pathogen-free male Wistar rats were randomly divided into control group,low-,medium-and high-dose crotonaldehyde groups,with 10 rats in each group.The crotonaldehyde solution at doses of 0.0,2.5,4.5,and 8.5 mg/kg body weight were given by intragastric administration,once a day,5 days per week,and continuous for 90 days.The body weight of the rats were weighed during the exposure period.After the exposure,the liver organ coefficients and histopathological changes of the rats were observed.The activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)and the level of total bilirubin(TBIL)in the serum of rats were determined by colorimetry.The levels of malondialdehyde(MDA)and reduced glutathione(GSH),and the activities of glutathione peroxide(GSH-Px)and superoxide dismutase(SOD)were determined by colorimetry.The levels of interleukin(IL)-1β,IL-6,tumor necrosis factor alpha(TNF-α)and interferon-γ(IFN-γ)was detected by enzyme-linked immunosorbent assay.Results At the end of exposure,the increment of body mass of rats in the low-,medium-and high-dose crotonaldehyde groups was lower than that in the control group(P<0.05).The organ coefficients of rats in the middle-and high-dose groups were lower than that in the control group(P<0.05).The liver tissues of the three doses crotonaldehyde groups showed varying degrees of inflammatory cell infiltration.The activities of ALT,AST and the level of TBIL in the serum of rats increased with the increase of the crotonaldehyde exposure dose(P<0.01).With the increase of the crotonaldehyde dose,the level of MDA in rat liver tissue increased(P<0.01),and the level of GSH and the activities of GSH-Px and SOD decreased(P<0.01).The levels of IL-1β,IL-6,TNF-αand IFN-γin rat liver tissues increased(P<0.05).Conclusion Crotonaldehyde exposure can cause liver tissue damage in rats.Its mechanism of action may b

关 键 词：巴豆醛 肝脏毒性 氧化应激 炎性因子 大鼠 剂量-效应关系 

分 类 号：R114[医药卫生—卫生毒理学] R135.1[医药卫生—公共卫生与预防医学]