| 郭滢森,刘皓然,祝宇,等.以斑马鱼为模型研究med15在脂质稳态中的作用及调控脂代谢药物的筛选[J].中国海洋药物,2026,(4):-. |
| 以斑马鱼为模型研究med15在脂质稳态中的作用及调控脂代谢药物的筛选 |
| Zebrafish as a model to study med15 in lipid homeostasis and drug screening for lipid metabolism |
| 投稿时间：2025-04-02 修订日期：2025-05-23 |
| DOI： |
| 中文关键词: med15 脂代谢 斑马鱼 药物筛选 |
| English Keywords:med15 lipid metabolism zebrafish drug screening |
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| 中文摘要: |
| 目的 以斑马鱼为模型探究med15在脊椎动物脂代谢中发挥的作用，进一步通过构建高脂模型筛选调控脂代谢的药物。方法 采用油红O染色法检测med15在维持斑马鱼脂质稳态中的作用；将转基因斑马鱼Tg(lfabf:dsRed; elaA:EGFP)与med15-/-斑马鱼交配，构建转基因med15突变体斑马鱼；利用显微镜观察med15突变体幼鱼肝脏的大小和形态、胚胎前24 hpf（hours post fertilization，受精后数小时）的发育情况及幼鱼体长；使用高脂培养液处理5 dpf（days post fertilization，受精后数天）幼鱼6 d构建高脂模型，检测药物Denifanstat及Fatostatin对脂质含量的影响。结果 med15突变体斑马鱼体内脂质含量明显降低；成功在转基因斑马鱼Tg(lfabf:dsRed; elaA:EGFP)基础上构建med15突变体斑马鱼，且其肝脏大小和形态与野生型相比无显著差异；med15突变体胚胎在前24 hpf发育较慢，且5 dpf幼鱼体长较短；Denifanstat和Fatostatin均能抑制高脂模型中的脂质累积。结论 med15在维持斑马鱼脂质稳态中发挥重要作用，是潜在的、重要的脂代谢药物作用靶点。斑马鱼高脂模型可有效用于筛选调控脂代谢的海洋小分子化合物。 |
| English Summary: |
| Objective This study uses zebrafish as a model to investigate the role of med15 in lipid metabolism in vertebrates and further screens for drugs that regulate lipid metabolism by establishing a high-fat model. Methods Oil Red O staining was employed to assess the function of med15 in maintaining zebrafish lipid homeostasis. Transgenic zebrafish Tg(lfabf:dsRed; elaA:EGFP) were crossed with med15-/- zebrafish to generate med15 mutant zebrafish. Microscopy was utilized to examine liver size and morphology, the developmental status of embryos up to 24 hpf (hours post fertilization), and the body length of larvae in med15 mutants. The high-fat model was established by treating 5 dpf (day post fertilization) zebrafish with high-fat culture medium for 6 days, simultaneously assessing the effects of the drugs Denifanstat and Fatostatin on lipid content. Results The med15 mutant zebrafish exhibited a significant reduction in lipid content. The med15 mutants were successfully established in the background of the transgenic zebrafish Tg(lfabf:dsRed; elaA:EGFP), with no significant differences in liver size or morphology compared to wild-type controls. The development of med15 mutant embryos was slower during the first 24 hpf, and the larvae at 5 dpf exhibited reduced body length. Both Denifanstat and Fatostatin effectively inhibited lipid accumulation in the high-fat model. Conclusion med15 plays a crucial role in maintaining lipid homeostasis in zebrafish and represents a potentially important drug target for lipid metabolism. The zebrafish high-fat model can be effectively utilized to screen marine small molecule compounds that regulate lipid metabolism |
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