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目的研究1,2-二氯乙烷(1,2-DCE)吸入染毒对SD大鼠肝脏的遗传损伤作用及代谢酶表达的影响。方法SPF级健康成年SD雄性大鼠30只,按体重随机分为对照组(n=8)、低剂量组(n=11)和高剂量组(n=11)。采用口鼻式动式吸入染毒法,低、高剂量组分别给予质量浓度为600和1 800 mg/m~3的1,2-DCE染毒8h/d,连续7d;对照组采取相同处理方式吸入正常空气。实验结束后,利用实时荧光定量PCR技术检测代谢酶及遗传损伤相关指标p53的m RNA表达改变。结果实时荧光定量PCR结果显示,1,2-DCE染毒后高剂量组大鼠肝脏中Ⅰ相代谢酶细胞色素P4502E1(CYP2E1)、乙醇脱氢酶1(ADH1)、乙醛脱氢酶3α1(ALDH3α1)、Ⅱ相代谢酶谷胱甘肽S-转移酶A1(GSTA1)、谷胱甘肽S-转移酶M1(GSTM1)、谷胱甘肽S-转移酶A3(GSTA3)以及遗传损伤相关基因p53 m RNA表达均被诱导升高,差异有统计学意义(P<0.05)。结论CYP2E1、ADH1、ALDH3α1、GSTA1、GSTM1和GSTA3是1,2-DCE的主要代谢酶,其表达量可以被1,2-DCE染毒诱导而发生改变,p53信号通路所介导的遗传损伤应激可能参与了1,2-DCE诱导大鼠肝细胞坏死或凋亡的过程。
Objective To study the effects of 1,2-dichloroethane (1,2-DCE) inhalation on the genetic damage and the expression of metabolizing enzymes in the liver of SD rats. Methods Thirty male SD rats were randomly divided into control group (n = 8), low dose group (n = 11) and high dose group (n = 11). Rats in low dose and high dose groups were treated with 1,2-DCE at a concentration of 600 and 1800 mg / m 3 for 8 h / d for 7 days, respectively. The control group received the same treatment Way to breathe the normal air. After the experiment, the real-time fluorescence quantitative PCR was used to detect the changes of m RNA expression of metabolic enzymes and p53, a marker of genetic damage. Results The results of real-time quantitative PCR showed that the levels of CYP2E1, ADH1 and ALD3α1 ALDH3α1), GSTA1, GSTM1, GSTA3 and genes related to genetic damage p53 m RNA expression was induced to rise, the difference was statistically significant (P <0.05). Conclusions CYP2E1, ADH1, ALDH3α1, GSTA1, GSTM1 and GSTA3 are the major metabolic enzymes of 1,2-DCE. The expression levels of CYP2E1, ADH1, GSTM1 and GSTA3 may be induced by 1,2-DCE exposure. It may be involved in 1,2-DCE induced hepatocyte necrosis or apoptosis in rats.