关键词: 斑马鱼, 急性肾损伤, 肾小管上皮细胞, 甲硝唑

Abstract:

Ｏｂｊｅｃｔｉｖｅ：To generate a transgenic zebrafish model of acute kidney injury（AKI）, which will be applied to studies of the mechanism of AKI, renal regeneration and small molecule screening.
Ｍｅｔｈｏｄｏｌｏｇｙ：Based on a bacterial nitroreductase (NTR) strategy to convert a prodrug, metronidazole (MTZ) into a cytotoxic metabolite. Tg (enpep: Ga l4) and Tg (UAS: NTRmCherry) were generated respectively. MTZ treatment in Tg (enpep: Ga l4;UAS: NTRmCherry) embryos at 2 days post fertilization (dpf) resulted in renal tubular epithelial cells (RTECs) injury and loss. Embryo pericardial edema ratio, proximal tubular epithelial cells marker gene slc20a1a in situ hybridization, reabsorption capacity and ultrastructure of proximal tubular were investigated and carried out.
Ｒｅｓｕｌｔｓ：(1) A transgenic zebrafish Tg (enpep:Ga l4) and Tg (UAS: NTRmCherry) was successfully generated, and the mCherry fluorescence was specifically presented in the pronephric tubule of Tg (enpep: Ga l4;UAS: NTRmCherry) embryos at 30 hours post fertilization. (2) Embryos edema ratio increased depending on MTZ treatment dosage and time course. (3) MTZ induced injury resulted in decreased expression of slc20a1a and proximal tubular reabsorption dysfunction. Transmission electron microscope imaging showed renal tubular epithelial cell destruction, detached brush border and microtubules in the lumen.
Ｃｏｎｃｌｕｓｉｏｎ：
The zebrafish model of AKI was established and could be applied to the mechanism of AKI, renal regeneration and small molecule screening.

Key words: zebrafish, acute kidney injury, renal tubular epithelial cells, metronidazole