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[目的]探讨饮用水有机提取物对大鼠肝脏代谢酶CYP1A2与CYP2E1酶活性及蛋白表达的影响,为当地饮用水有机物污染的安全性评价及肝脏毒性机制的阐明提供依据。[方法]采用固相萃取法提取水样中有机污染物,40只SD大鼠随机分成4组,分别为对照组(玉米油)和低、中、高3个染毒组[剂量分别为5、20、80 L/(kg·d)],经口灌胃亚慢性染毒(12周)。荧光分光光度法和活性比色法分别测定CYP1A2与CYP2E1酶活性。采用Western blot法检测CYP1A2、CYP2E1的蛋白质表达水平。[结果]与对照组相比,高剂量组的CYP1A2酶活性明显升高,差异具有统计学意义(P<0.05);CYP2E1酶活性在中、高剂量组均明显升高(P<0.05)。随着染毒剂量的增加,CYP1A2的蛋白表达量在高剂量组升高(P<0.05);与对照组相比,CYP2E1的蛋白表达量在中、高剂量组均增加,差异具有统计学意义(P<0.05)。[结论]该地较高剂量的饮用水有机提取物可上调CYP1A2及CYP2E1的蛋白质表达,从而诱导CYP1A2和CYP2E1酶活性的增强。此可能为饮用水有机提取物肝脏毒性的重要机制之一。
[Objective] To investigate the effects of organic extracts of drinking water on enzyme activities and protein expressions of hepatic metabolic enzymes CYP1A2 and CYP2E1 in rats, and to provide evidence for the safety evaluation of local drinking water organic pollutants and elucidation of liver toxicity mechanisms. [Method] Solid-phase extraction was used to extract organic pollutants from water samples. Forty SD rats were randomly divided into four groups: control group (corn oil) and low, medium and high dose groups [dose of 5 , 20,80 L / (kg · d)], sub-chronic oral administration of oral toxicity (12 weeks). The activities of CYP1A2 and CYP2E1 were determined by fluorescence spectrophotometry and colorimetric assay, respectively. The protein expression levels of CYP1A2 and CYP2E1 were detected by Western blot. [Result] The CYP1A2 activity in high dose group was significantly higher than that in control group (P <0.05). The activity of CYP2E1 in middle and high dose group was significantly increased (P <0.05). Compared with the control group, the protein expression of CYP2E1 increased in the medium and high dose groups as the exposure dose increased, the protein expression of CYP1A2 increased in the high dose group (P <0.05), the difference was statistically significant (P <0.05). [Conclusion] The higher dose of organic extract from drinking water could up-regulate the protein expression of CYP1A2 and CYP2E1 and induce the enhancement of CYP1A2 and CYP2E1 activities. This may be one of the important mechanisms of liver toxicity of organic extracts of drinking water.