三氯乙烯对肝细胞代谢酶基因与凋亡基因表达的影响

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目的:探讨三氯乙烯(trichloroethylene,TCE)对人L02肝细胞代谢酶基因CYP1A2、CYP3A4、CYP2E1和凋亡基因BAX、BAD、Bcl-2 mRNA表达水平的影响。方法:以1%二甲亚砜(DMSO)为溶剂对照,用不同浓度TCE(0.25、0.5、1.0和2.0mmol/L)染毒L02肝细胞24h,另外用同一浓度1.0mmol/L TCE染毒细胞3~24h,采用实时荧光定量PCR(real-time quantitative PCR)技术检测L02肝细胞中CYP1A2、CYP3A4、CYP2E1和凋亡基因BAX、BAD、Bcl-2 mRNA的表达。结果:不同剂量TCE染毒后CYP1A2、CYP3A4、CYP2E1 mRNA表达明显上升,CYP1A2升高36%~726%,CYP3A4升高56%~525%,CYP2E1升高15%~94%,与对照组比较,差异均有统计学意义(P<0.05或P<0.01);凋亡基因BAX、BAD、Bcl-2表达水平也明显升高,与对照组比较差异均有统计学意义(P<0.05或P<0.01)。用1.0mmol/L TCE染毒3~24h,同样发现肝代谢酶基因和凋亡基因表达增加,与对照组比较差异均有统计学意义(P<0.05或P<0.01)。结论:TCE可诱导L02肝细胞中代谢酶基因及凋亡基因表达变化,肝代谢酶基因和凋亡基因可能在TCE对肝细胞毒性效应中发挥重要作用。 Objective: To investigate the effects of trichlorethylene (TCE) on the expression of CYP1A2, CYP3A4, CYP2E1 and BAX, BAD and Bcl-2 mRNA in human L02 hepatocytes. Methods: L02 hepatocytes were exposed to different concentrations of TCE (0.25, 0.5, 1.0 and 2.0 mmol / L) for 24 h with 1% dimethylsulfoxide (DMSO) Cells were cultured for 3-24 hours. The expression of CYP1A2, CYP3A4, CYP2E1 and apoptosis genes BAX, BAD and Bcl-2 in L02 hepatocytes were detected by real-time quantitative PCR. Results: The mRNA expression of CYP1A2, CYP3A4 and CYP2E1 increased significantly after TCE exposure, with the increase of CYP1A2 36% -726%, CYP3A4 56% -525%, and CYP2E1 15% -94%. Compared with the control group, (P <0.05 or P <0.01). The expressions of BAX, BAD and Bcl-2 were also significantly higher than those in control group (P <0.05 or P < 0.01). With 1.0mmol / L TCE exposure for 3 ~ 24h, the expression of hepatic metabolic enzyme gene and apoptosis gene were also found to be increased, which were significantly different from the control group (P <0.05 or P <0.01). CONCLUSION: TCE can induce the changes of the expression of metabolic enzyme genes and apoptotic genes in L02 hepatocytes. The hepatic metabolic enzyme genes and apoptosis genes may play an important role in hepatotoxicity induced by TCE.
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