常山碱盐斑马鱼胃肠道毒性及其评价

Research on Gastrointestinal Toxicity Evaluation of Dichroa Alkali Salt in Zebrafish

为了分析常山碱盐的胃肠道毒性,并探寻适合此类毒性药物的模式动物,以斑马鱼为研究对象,测定常山碱盐对斑马鱼的10%致死浓度(LC_(10),以质量浓度计)和最大非致死浓度(MNLC,以质量浓度计),并应用斑马鱼肠蠕动抑制作用评价模型对常山碱盐的肠道毒性作用进行评价,包括肠蠕动抑制评价、肠道表型和肠道病理组织学观察.结果表明,常山碱盐对斑马鱼的LC_(10)和MNLC约为10 mg/L和5 mg/L.在0.50,1.67,5.00,10.00 mg/L质量浓度常山碱盐处理条件下,斑马鱼肠道内容物含量明显增加,肠蠕动抑制率分别为27.78%,61.11%,77.11%,80.89%,常山碱盐对斑马鱼肠蠕动有较明显的抑制作用.肠道毒性表型和病理组织学观察发现,在0.50,1.67,5.00,10.00 mg/L质量浓度常山碱盐处理条件下,斑马鱼肠道褶皱减少或消失,肠道黏膜细胞变性,肠道黏膜破坏,肠腔模糊,肠腔变窄,且严重程度和发生率与常山碱盐质量浓度呈较明显的正相关性.常山碱盐存在明确的胃肠道毒性,斑马鱼可作为模式动物应用于消化道毒性药物的致毒作用研究.

To systematically analyze the gastrointestinal toxicity of dichroa alkali salt and explore the model animals suitable for such toxic drugs, the LC_(10)and MNLC of dichroa alkali salt in zebrafish were observed.The intestinal effects of dichroa alkali salt were evaluated by the zebrafish model, including evaluation of intestinal peristalsis inhibition, intestinal phenotype, and tissue pathology of intestinal tract.Results showed that the LC_(10)and MNLC of dichroa alkali salt on zebrafish were about 10 μg/mL and 5 μg/mL,respectively.Zebrafish were treated by dichroa alkali salt with concentration of 0.5,1.67,5 and 10 μg/mL,and the intestinal contents of zebrafish increased significantly.The inhibition rates of intestinal peristalsis were 27.78%,61.11%,77.11% and 80.89%,respectively, which showed that all concentrations of dichroa alkali salt has obvious inhibitory effect on the intestinal peristalsis of zebra fish.The intestinal toxicity phenotype and histopathological observation showed that under the conditions of 0.5,1.67,5 and 10 μg/mL salt treatment, the intestinal folds were reduced or disappeared, the intestinal mucosa cells were denaturated, the intestinal mucosa was destroyed, the intestinal lumen was blurred, and the intestinal lumen was narrowed, and the severity was positively correlated with the incidence.Above all, dichroa alkali salt presents definite gastrointestinal toxicity.Zebrafish can be used as a model animal to systematically study the toxic effects and characteristics of gastrointestinal toxic drugs.