硫芥子气(SM,二氯二乙基硫醚)是一种强效的腐蚀性化学毒物,可引起肺肺,人类皮肤和眼部疾病并发症。目前,SM没有指定的补救措施,其操作的毒理学过程仍未确认。这项工作采用斑马鱼作为模型生物来研究暴露于SM的毒性表现和机制,旨在为预防和治疗这种疾病提供新的见解。结果表明,SM导致斑马鱼幼虫的存活率降低(LC50=2.47mg/L),孵化率的降低,心包面积的增加,和小头综合症。然而,T-5224(c-Fos/激活蛋白的选择性抑制剂)降低了死亡率(LC50=2.79mg/L),孵化率的降低,以及形态变化的恶化。我们发现SM会导致斑马鱼幼虫的软骨发育障碍。逆转录-定量聚合酶链反应发现SM增加炎症相关基因的表达(IL-1β,IL-6和TNF-α)和显着增加的软骨发育相关基因表达(fosab,mmp9和atf3)。然而,SOX9a的表达,sox9b,Col2a1a减少。蛋白质水平检测还发现c-fos蛋白表达增加和COL2A1表达显著降低。然而,T-5224也减轻了基因表达的变化,和SM暴露引起的蛋白质水平。这项研究的结果表明,SM诱导的斑马鱼软骨发育障碍与c-Fos/AP-1通路密切相关。
Sulfur mustard (SM, dichlorodiethyl sulfide) is a potent erosive chemical poison that can cause pulmonary lung, skin and eye disease complications in humans. Currently, there is no designated remedy for SM, and its operation\'s toxicological process remains unidentified. This work employed zebrafish as a model organism to investigate the toxic manifestations and mechanisms of exposure to SM, aiming to offer novel insights for preventing and treating this condition. The results showed that SM caused a decrease in the survival rate of the zebrafish larvae (LC50 = 2.47 mg/L), a reduction in the hatching rate, an increase in the pericardial area, and small head syndrome. However, T-5224 (a selective inhibitor of c-Fos/activator protein) attenuated the reduction in mortality (LC50 = 2.79 mg/L), the reduction in hatching rate, and the worsening of morphological changes. We discovered that SM causes cartilage developmental disorders in zebrafish larvae. The reverse transcription-quantitative polymerase chain reaction found that SM increased the expression of inflammation-related genes (IL-1β, IL-6, and TNF-α) and significantly increased cartilage development-related gene expression (fosab, mmp9, and atf3). However, the expression of sox9a, sox9b, and Col2a1a was reduced. The protein level detection also found an increase in c-fos protein expression and a significant decrease in COL2A1 expression. However, T-5224,also and mitigated the changes in gene expression, and protein levels caused by SM exposure. The results of this study indicate that SM-induced cartilage development disorders are closely related to the c-Fos/AP-1 pathway in zebrafish.