Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.
Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.
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急性肾衰竭心脏并发症药物筛选模型的建立
DOI：
10.3390/biom11091370
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发表时间：
2021-09-16
期刊：
影响因子：
5.5
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Liao S;Yang W;Yu T;Dai L;Liu X;Zhang J;Zhao J;Liu C
急性肾功能衰竭（acute renal failure，ARF）是一种以肾功能迅速、严重下降为特征的临床危重综合征。ARF的并发症，尤其是心脏并发症（3型心肾综合征，CRS-3）是ARF患者死亡的主要原因。然而，治疗药物的短缺和有限的疗效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，我们构建了一株能特异性消融肾小管上皮细胞的转Tg（cdh 17：Dendra 2-NTR）基因斑马鱼细胞系。斑马鱼幼鱼缺乏肾小管上皮细胞可导致ARF。ARF的症状，如心脏增大、心率减慢和血瘀，与人CRS-3的临床表现相似。此外，临床上常用的两种治疗心力衰竭的药物（地高辛和依那普利）也有效缓解了斑马鱼CRS-3的症状，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，为大规模筛选治疗其并发症的新药奠定了基础。
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.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Lekawanvijit S
影响因子：
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作者：
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