1,2-二氯乙烷诱导SD大鼠肝脏Ⅰ相代谢酶基因差异表达研究

Acute 1,2-dichloroethane exposure induced differential gene expression of liver phaseⅠmetabolic enzymes in SD rats

目的探讨1,2-二氯乙烷(1,2-DCE)急性吸入染毒对大鼠肝脏Ⅰ相代谢酶基因差异表达的影响。方法无特定病原体级SD大鼠随机分为对照组(16只)、低剂量组和高剂量组(各24只),雌雄各半。采用口鼻式动式吸入染毒法,低、高剂量组大鼠每天分别予剂量为600、1 800 mg/m^3的1,2-DCE染毒8 h,连续7 d,对照组大鼠予吸入新鲜空气。染毒结束后,采用实时荧光定量聚合高剂量组酶链反应法检测大鼠肝组织中细胞色素P450 2E1氧化酶(CYP2E1)、乙醇脱氢酶1(ADH1)与乙醛脱氢酶3α1(ALDH3α1)基因mRNA的相对表达水平。结果雄性高剂量组大鼠CYP2E1的相对表达水平高于雄性低剂量组和雌性高剂量组(P<0.05)。雄性低、高剂量组大鼠ADH1的相对表达水平均高于雄性对照组(P<0.05),雄性高剂量组大鼠ADH1的相对表达水平高于雄性低剂量组和雌性高剂量组(P<0.05)。高剂量组大鼠ALDH3α1相对表达水平分别高于对照组和低剂量组(P<0.05)。结论高剂量1,2-DCE染毒可导致大鼠肝脏Ⅰ相代谢酶表达增加,对雄性大鼠影响较雌性明显。

Objective To investigate the effect of 1,2-dichloroethane(1,2-DCE)acute inhalation exposure on the differential gene expression of phaseⅠmetabolic enzymes.Methods The specific pathogen free SD rats were randomly divided into control group(16 rats),low-and high-dose groups(24 rats in each group,half males and half females).Low-and high-dose group were given daily 600,1 800 mg/m3 of 1,2-DCE,and the control group given the fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days.After the end of exposure,the relative mRNA expression of cytochrome P450 2 E1(CYP2 E1),alcohol dehydrogenase(ADH1)and acetaldehyde dehydrogenase 3 alpha 1(ALDH3α1)in the liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The relative expression of CYP2 E1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05).The relative expression of ADH1 in male low-and high-dose groups was higher than that in male control group(P<0.05).The relative expression of ADH1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05).The relative expression of ALDH3α1 in high-dose group was higher than that in control group and low-dose group(P<0.05).Conclusion High dose 1,2-DCE could increase the gene expression of phaseⅠmetabolic enzymes in rat liver.The 1,2-DCE has more obvious effect in male rats than in female rats.