Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.

中文翻译：

---

急性肾衰竭心脏并发症药物筛选模型的建立


急性肾衰竭（ARF）是一种肾功能快速而严重下降的临床危重综合征。 ARF的并发症，特别是心脏并发症（心肾综合征3型，CRS-3），是ARF患者死亡的主要原因。然而，治疗药物的短缺和疗效有限使得建立新的大规模药物筛选模型具有重要意义。基于硝基还原酶/甲硝唑（NTR/MTZ）细胞消融系统，我们构建了Tg（cdh17：Dendra2-NTR）转基因斑马鱼系，可以特异性消融肾小管上皮细胞。斑马鱼幼虫肾小管上皮细胞的缺乏会导致 ARF。 ARF的症状如心脏扩大、心率缓慢、血瘀等，与人类CRS-3的临床表现相似。此外，临床治疗心力衰竭常用的两种治疗药物（地高辛和依那普利）也能有效缓解斑马鱼的CRS-3症状，证明了该模型的有效性。药物筛选进一步发现了一种潜在的候选药物——α-硫辛酸，它可以通过其抗氧化功能有效缓解CRS-3的症状。据此，我们建立了一种新的斑马鱼ARF模型，为大规模筛选针对其并发症的新治疗药物奠定了基础。