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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1000ppm1-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-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 investigate the hepatotoxicity of 1-bromopropane in two male rats and the role of glutathione S-transferase (GST) in detoxification of liver. Methods Eighteen Fischer344 rats and 18 Wistar rats were randomly divided into two groups. One group was given fresh air and the other group was given 1000ppm 1-bromopropane for 8 hours a day for 4 weeks. The liver function and morphology were evaluated by biochemical and pathological sections of plasma. GST viability and gene expression levels in the liver were measured by chemical colorimetry and real-time quantitative PCR. Results Exposure of 1-bromopropane induced weight loss and liver weight gain in both rats. The pathological findings showed that the hepatocytes around the central veins of the liver had vacuolar changes, and the levels of CK, ALT, TBIL and DBIL in plasma increased significantly. GST activity in the cytoplasm of both rat liver cells increased, and the activity of GST in the Fischer344 rat microsome also increased. The expression of GST mRNA in the liver increased. Conclusion 1-bromopropane exposure has liver toxicity to both male rats, and GST may play an important role in the detoxification metabolism of 1-bromopropane in the liver.