ZnCl_2对二甲基甲酰胺所致小鼠急性肝毒性的保护作用研究  

Protective Effects of ZnCl_2 on Acute Liver Toxicity Induced by N,N-dimethylformamide in Mice

作　　者：王福强[1] 王德伟[1] 阮明[1] 贾凤兰[1] 张宝旭[1] 

机构地区：[1]北京大学医学部,北京100191

出　　处：《工业卫生与职业病》2008年第5期261-264,F0004,共5页Industrial Health and Occupational Diseases

基　　金：北京市自然科学基金资助项目(7072042)

摘　　要：目的研究ZnCl2对二甲基甲酰胺(N,N-dimethylformamide,DMF)致小鼠急性肝损伤的保护作用,为保护DMF接触人群提供指导。方法将80只动物随机分为8组:正常对照组、DMF组、ZnCl2-10+DMF组、ZnCl2-20+DMF组、ZnCl2-40+DMF组、ZnCl2-10组、ZnCl2-20组和ZnCl2-40组。所有ZnCl2给药组每天皮下注射一定剂量的ZnCl2溶液。ZnCl2-10、ZnCl2-20和ZnCl2-40组在DMF染毒之前,其余组在DMF染毒后48 h处死小鼠,测定其血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH)的活力;制备肝匀浆,测定ZnCl2-10、ZnCl2-20和ZnCl2-40组小鼠肝金属硫蛋白(MT)含量;留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化。结果与正常组比较,DMF组小鼠血清中ALT、AST和LDH活力明显升高,肝脏组织出现明显的肝细胞变性坏死;ZnCl2+DMF组的小鼠血清中ALT、AST和LDH活力与DMF组相比明显降低,肝脏组织病理损伤明显减轻。单独给予ZnCl2组小鼠MT含量升高。结论ZnCl2对DMF引起的小鼠急性肝损伤具有明显的保护作用。Objective To investigate the protective effects of ZnCl2 on acute hepatic injury induced by N, N-dimethylformamide （DMF） in mice so as to provide guidance in protecting DMF exposed workers. Methods 80 mice were randomly divided into eight groups, e.g. normal control group, DMF group, ZnCl2- 10-DMF group, ZnCl2-20＋DMF group, ZnCl2 40＋DMF group, ZnCl2-10 group, ZnCl2-20 group, and ZnCl2-40 group. The mice were subcutaneously injected with certain dosages of ZnCl2 or saline in consecutive days. The mice of ZnCl2 groups were sacrificed before the DMF exposure and the mice in ZnCl2 ＋ DMF groups were sacrificed at 48 h after the exposure. Blood samples were collected for the determination of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and lactic dehydrogenase （LDH） activities in serum. Liver samples were also collected for the MT measurement and histological observation after stained with hematoxylin and eosin （HE）. Results All the parameters, ALT, AST and LDH, of DMF exposed groups increased significantly and obvious denatured hepatic cell necrosis was found in liver tissues in comparison with the control group. However, these parameters of ZnCl2 ＋DMF groups lowered significantly in comparison with the DMF groups and the pathological damages of the liver tissues decreased significantly. The MT concentration increased significantly in single ZnCl2 groups and ZnCl2 ＋ DMF groups. Conclusions These findings suggest that ZnCl2 showed significant protective effects on DMF induced acute liver damages in mice.

关 键 词：ZNCL2 二甲基甲酰胺 急性肝损伤 金属硫蛋白 

分 类 号：R114[医药卫生—卫生毒理学]