Chenglong Ma , Yanan He , Huan Wang , Xu Chang , Chelimuge Qi , Yuanzhou Feng , Xiaoxu Cai , Meirong Bai , Xueyan Wang , Baoquan Zhao , Wu Dong
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引用次数: 0
摘要
Gelsemium elegans(GE),又名 Duanchangcao,是一种与腹部中毒症状有关的植物;然而,GE 的毒性仍然未知。Gelsemine(GEL)是从GE中提取的一种生物碱,是毒性最强的生物碱之一。本研究以斑马鱼为动物模型,采用高通量基因测序技术来鉴定与GEL毒性相关的基因和信号通路。暴露于 GEL 会对斑马鱼幼体的心率、鳔发育和活动产生负面影响。转录组学数据揭示了炎症和吞噬细胞信号通路的富集。RT-PCR 分析表明,由于暴露于 GEL,胰腺相关基因(包括胰腺凝固蛋白酶 (Ctr) 家族,如 Ctrl、Ctrb 1 和 Ctrc)的表达量减少。此外,暴露于 GEL 会显著降低 Ctrb1 蛋白的表达,同时提高斑马鱼幼体的胰蛋白酶和血清淀粉酶活性。GEL 还导致转基因斑马鱼的胰腺相关荧光面积减少,中性粒细胞相关荧光面积增加。这项研究揭示了 GEL 对斑马鱼幼体的毒性与急性胰腺炎症有关。
Understanding the toxicity mechanism of gelsemine in zebrafish
Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.
期刊介绍:
Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.