摘要:
微囊藻毒素-LR (microcystin-LR,MC-LR)是分布最广泛和毒性最强的一种微囊藻毒素,对水生动物造成潜在的健康威胁。大量科学研究证实,动物体中的细胞色素P450酶(CYP)参与内源性物质及外源毒性物质的代谢过程。为探究两栖动物生殖器官中的CYP酶对低剂量MC-LR生殖毒效应的调节作用,选择雄性黑斑蛙(Rana nigromaculata)为受试动物,采用静态置换法和体内暴露方法,分别暴露于0、0.1、1和10 μg·L-1 MC-LR溶液0、7和14 d;用实时荧光定量PCR方法检测精巢中CYP46A1、CYP2H2和CYP2G1的mRNA表达水平。结果表明,暴露于0.1、1和10 μg·L-1 MC-LR 14 d后,CYP46A1在mR-NA水平分别上调了1.86、1.65和1.22倍,CYP2H2在mRNA水平分别上调了4.62、1.80和1.04倍,CYP2G1的mRNA水平分别上调了2.63、2.16和1.56倍。MC-LR在1 μg·L-1剂量下暴露7 d后,CYP46A1、CYP2H2和CYP2G1 mRNA水平均出现显著上调。上述研究表明,微囊藻毒素对黑斑蛙精巢3种CYP基因在mRNA水平上都存在低剂量刺激效应。低剂量MC-LR能诱导黑斑蛙精巢中CYP46A1转录水平变化,促进胆固醇转化为24S-羟化胆固醇,潜在破坏雄性黑斑蛙精巢中胆固醇水平的平衡;MC-LR也能够诱导精巢中CYP2H2和CYP2G1转录水平的变化,潜在调节CYP2H2和CYP2G1转录水平,进而影响MC-LR的代谢作用。
Abstract:
Extensive studies have confirmed that cytochrome P450 enzyme (CYP) played a key role in the metabo-lism process of endogenous and exogenous toxic substances in animals. Microcystin-LR (MC-LR), the most common and toxic compound among the microcystin isoforms, is ubiquitous in water body and poses great threats to aquatic organisms. In this study, to investigate the effects of CYP enzymes on the reproductive toxicity of low-dose MC-LR to amphibian testis tissue, the male Rana nigromaculata were exposed to 0, 0.1, 1 and 10 μg·L-1 MC-LR for 0, 7 and 14 d, respectively. Significant up-regulation was observed for the mRNA levels of CYP46A1, CYP2H2 and CYP2G1 in the treatment of 1 μg·L-1 MC-LR for 7 d. After 14-d exposure to 0.1, 1 and 10 μg·L-1 MC-LR, the mRNA levels were up-regulated by 1.86, 1.65, and 1.22 folds for CYP46A1, 4.62, 1.80, and 1.04 folds for CYP2H2, and 2.63, 2.16, and 1.56 folds for CYP2G1, respectively. Hormesis effects happened in the treatment of male frog by MC-LR. From these results, we speculated that low-dose MC-LR might promote the transformation of cholesterol to 24S-hydroxy cholesterol and thus cause cholesterol homeostasis distorted through modulating the transcription levels of CYP46A1 in the testis of male Rana nigromaculata. In addition, the changes in the transcription levels of CYP2H2 and CYP2G1 might be related to the metabolism of MC-LR.
点击查看大图
下载:
