Nrf2和Keapl mRNA表达在燃煤型砷中毒肝损伤中作用

Effects of Nrf2 mRNA and Keapl mRNA expressions on arsenism liver injury caused by coal-burning

目的探讨Nrf2和Keapl mRNA表达在燃煤型砷中毒肝损伤中的作用。方法选择贵州省燃煤污染型砷中毒病区133例砷暴露者为砷暴露组(包括病区非病人组、无明显肝病组、轻度和中重度肝病组),以非砷污染村34名健康居民为对照组;实时荧光定量PCR检测外周血Nrf2和Keapl mRNA表达,化学法检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、硫氧还蛋白还原酶(TrxR)活力和丙二醛(MDA)含量。结果对照组、病区非病人组、无明显肝病组、轻度和中重度肝病组Nrf2 mRNA表达量分别为0.650 5、0.690 4、0.877 8、1.283 4和1.393 5,Keapl mRNA表达量分别为1.569 1、1.451 0、1.395 4、1.048 9和0.882 0;与对照组、病区非病人组和无明显肝病组比较,轻度和中重度肝病组Nrf2 mRNA表达上调,Keapl mRNA表达下调,SOD活力降低(P<0.05);中重度肝病组GSH-Px和TrxR活力降低,MDA含量升高(P<0.05)。Nrf2 mRNA表达与酶活力呈负相关、与MDA含量呈正相关,Keapl mRNA表达与酶活力呈正相关(P<0.05)。结论燃煤砷可能通过调控Nrf2和Keapl mRNA表达量,调节机体氧化应激水平,参与砷中毒肝损伤的发生发展。

Objective To invesigate the effects of transcriptional expressions of nuclear factor-erythroid 2-related factor 2（Nrf2） and Kelch-like ECH-associated protein 1（Keapl） on the development of liver injury in endemic arsenism caused by coal-burning.Methods Totally 133 residents with arsenic exposure were selected as arsenic exposure groups（including the normal group from endemic area,no obvious hepatopathy group,mild,moderate,and severe hepatopathy group）from the area with endemic arsenism in Guizhou province.Another 34 healthy residents were selected as the control group.The mRNA expressions of Nrf2 and Keapl were detected with real-time fluorescence quantitative PCR.Activities of superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）,thioredoxin reductase（TrxR）,and malondialdehyde（MDA） content were detected with chemical methods.Results The mRNA relative expressions of Nrf2 were 0.650 5（0.502 2-1.252 2）,0.690 4（0.602 7-1.040 5）,0.877 8（0.611 3-1.656 2）,1.283 4（0.761 1-2.765 9）,and 1.393 5（0.824 3-3.098 3） for control group,normal group from the endemic area,no obvious hepatopathy group,mild,and moderate-severe hepatopathy group and the mRNA relative expressions of Keapl for the 5 groups were 1.569 1（1.135 8-3.981 4）,1.451 0（1.123 7-3.015 2）,1.3954（1.170 0-2.706 9）,1.048 9（0.560 5-2.172 5）,and 0.882 0（0.512 6-1.503 1）,respectively.Compared with the control group,normal group from the endemic area,and no obvious hepatopathy group,the mRNA relative expressions of Nrf2 were upregulated in the mild and moderate-severe hepatopathy group,however,the mRNA relative expressions of Keapl downregulated and SOD activity decreased（P0.05 or P0.01）.The activities of GSH-Px and TrxR decreased in the moderate-severe hepatopathy groups,however,MDA content increased obviously（P0.05 or P0.01）.The correlation analyses showed that the transcriptional expressions of Nrf2 were inversely correlated with enzyme activities,and positively correlated with MDA content（P0.05 or P0.01）.The transcriptional expressions of Keapl were positively correlated with enzyme activities（P0.05 or P0.01）.Conclusion Arsenic may affect the levels of oxidative stress via regulating transcriptional expressions of Nrf2 and Keapl,and may be involved in the development of arsenism liver injury.