摘要:
磺胺类药物在环境中的普遍残留引起了人们对其潜在效应的担忧。因为磺胺混合物的效应不能通过单个物质效应进行准确预测,所以需要针对混合物效应开展深入研究。将秀丽线虫暴露于4种常用磺胺药物(磺胺嘧啶、磺胺吡啶、磺胺甲噁唑和磺胺甲嘧啶)组成的、环境浓度水平(0.01 mg·L-1)的混合物后,对生长调控基因dbl-1和egl-4,饮食调控基因eat-2和eat-18,过氧化氢酶(CAT)编码基因ctl-2和ctl-3,寿命调控基因sir-2,以及凋亡调控基因ced-4的表达水平进行检测。暴露组与空白对照组的结果比较表明,秀丽线虫dbl-1表达水平没有显著变化(下调3%),egl-4表达下调18%,解释了生长的抑制效应(抑制率为15.6%)。eat-2和eat-18的表达水平下调幅度相似,介于20%~22%之间,该幅度高于饮食的抑制效应(10.7%)。ctl-2和ctl-3的表达水平上调,分别比空白对照组高101%与66%,该幅度显著小于0.01 mg·L-1磺胺混合物暴露对CAT活性的刺激效应(比空白对照组高789.5%)。此外,sir-2的表达水平没有显著变化,与线虫寿命没有受到显著影响相一致。同时,ced-4表达上调32%,预示凋亡水平的显著增加。egl-4、eat-2、ctl-2和ced-4基因表达水平的显著变化分别表明磺胺混合物对β转化生长因子(TGF-β),烟酰乙酰胆碱受体(n AChR)、抗氧化系统以及细胞凋亡等多个方面的产生影响。
Abstract:
The ubiquitous existence of sulfonamide residues in environments is drawing attentions on their potential effects. Previously,mixture effects of sulfonamides were falsely predicted by simply combining the individual effects. Accordingly,direct investigations on sulfonamide mixture effects are needed. Here,Caenorhabditis elegans was exposed to mixtures containing four commonly used sulfonamides(sulfadiazine,sulfapyridine,sulfamethaxozale and sulfamethazine) at environmental relevant concentration of 0.01 mg·L-1. The expression levels of growth regulating genes(dbl-1 and egl-4),feeding regulating genes(eat-2 and eat-18),catalase(CAT) encoding genes(ctl-2 and ctl-3),lifespan regulating gene(sir-2) and apoptosis regulating gene(ced-4) were analyzed. Compared with the control,dbl-1 expressions in exposure to sulfonamide mixture were not significantly influenced with a slight down-regulation by 3%. Meanwhile,egl-4 expressions were down-regulated by 18%,explaining inhibitions on growth which was 15.6% lower than the control. Both eat-2 and eat-18 expressions were down-regulated by 20%~22%,greater than the inhibition on feeding(10.7% lower than the control). ctl-2 and ctl-3 expressions were up-regulated by 101% and 66% higher than the control,respectively. The up-regulation levels were significantly lower than the CAT stimulations which were 789.5% higher than the control. sir-2 expression was not significantly influenced as well as the lifespan. In addition,ced-4 expression was up-regulated by 32%,indicating increases in apoptosis. The results of egl-4,eat-2,ctl-2 and ced-4 indicated that the involvement of transforming growth factor β(TGF-β) pathway,nicotinic acetylcholine receptor(n AChR),antioxidant responses and apoptosis in the sulfonamide mixture effects,respectively.
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