目的研究1-溴丙烷对两种雄性大鼠的肝脏毒性及谷胱甘肽S-转移酶(GST)在肝脏解毒代谢中的作用。方法将18只Fischer344大鼠和18只Wistar大鼠分别随机分为两组,一组给予新鲜空气,一组给予1000ppm 1-溴丙烷,每天8h,连续暴露4周。通过血浆的生化指标和病理切片对肝脏的功能和形态进行了评价。利用化学比色法和实时定量PCR法对肝脏中的GST的活力和基因表达水平进行测量。结果1一溴丙烷暴露可引起两种大鼠体重的下降及肝脏重量的上升;病理发现肝脏中央静脉周围的肝细胞出现空泡样改变,血浆中CK、ALT和TBIL和DBIL等指标上升明显;两种大鼠肝脏细胞胞浆的GST活力增强,Fischer344大鼠微粒体GST的活力也增强;肝脏组织的GSTmRNA表达水平升高。结论1-溴丙烷暴露对两种雄性大鼠具有肝脏毒性,GST在1-溴丙烷的肝脏解毒代谢中可能起到较重要作用。
Objective To explore the hepatotoxicity of 1-bromopropane through inhalation and the role of glutathione Stransferase (GST) in the metabolism of 1-bromopropane in male rats. Methods Eighteen Fischer 344 male rats and 18 Wistar male rats were randomly divided into two groups, respectively, the rats in control group were given fresh air, the rats in experimental group were exposed to 1000 ppm 1-bromopropane contaminated air eight hours per day for 4 weeks. At the end of experiment, various biochemical parameters including plasma hepatic function indices and histopathological changes in liver were examined. Meanwhile , the activity and mRNA expression of GST in liver were also determined by eolorimetric method and real time quantitative PCR. Results After 4 week exposure, body weights of all exposed rats were decreased significantly, whereas the weights of livers were increased. Histopathological examination showed that obvious vaeuolation appeared around the central veins of liver in all the exposed rats; the levels of CK, ALT, TBIL and DBIL in plasma of exposed rats were increased; the cytosolie GST activity in liver of all exposed rats and the activity of mierosomal GST in liver of Fischer 344 exposed rats were significandy higher than that of controls. Additionally, the expression of GST mRNA was also enhanced by exposure to 1-bromopropopane. Conclusions The results showed that 1-bromopropane has definite hepatotoxicity in Fischer 344 and Wistar male rats, and GST might be involved in the detoxifieation of 1-bromopropane.