順鉑對斑馬魚仔魚側線毛細胞和皮膚離子細胞之影響

Abstract

摘要 Cisplatin在臨床上是最廣泛用於治療惡性腫瘤的藥物之一。然而，cisplatin常會造成的副作用包括腎毒性和耳毒性的傷害。斑馬魚已經被廣泛用來作為模式動物，研究藥物對胚胎發育以及生理功能的影響。過去研究發現cisplatin對斑馬魚側線毛細胞也會造成傷害，因此利用斑馬魚作為研究毛細胞的毒理模式。然而，目前仍未有研究利用斑馬魚去探討cisplatin的腎毒性。斑馬魚胚胎皮膚上分布數種離子細胞與哺乳動物腎臟上皮細胞有許多相似之處，因此本實驗想探討cisplatin對於斑馬魚離子細胞的影響。分析cisplatin對斑馬魚胚胎毛細胞與離子細胞的發育與功能的影響結果顯示，短時間處理濃度500 μM cisplatin 30分鐘後，顯著抑制斑馬魚胚胎側線毛細胞上的機械通道鈣離子流入，顯示毛細胞的功能受損。胚胎處理10 μM cisplatin四天後，毛細胞鈣離子流不但下降，而且毛細胞數目也顯著減少。在離子細胞的部分，處理1000 μM cisplatin 30分鐘後，會顯著降低離子細胞的排酸能力。同時離子細胞的粒腺體染色(??)性降低，顯示粒線體受到損傷。處理100 μM cisplatin 4天後，不但胚胎排酸量顯著受到抑制，也發現離子細胞數目減少。Cisplatin is a clinical drug for the treatment of cancer but it usually causes severe side-effects including nephrotoxicity and ototoxicity. Zebrafish has been an animal model to study the toxicity of drugs and small compounds. The purpose of this study isto examine the effects of cisplatin on the development and function of skin hair cells (HCs) and ionocytes (ICs) which are respectively similar to mammalian inner-ear HCs and renal ICs. The cell number of ICs and H+secretion by ICs weresignificantly suppressed by 0-96 hpf treatment of 10 µM and 100 µMcisplatin. Acute exposure to1 mM cisplatin for 30 min significantly suppressed H+ secretion by ICs. The mitochondria staining of ICs were significantly reduced by 30 min treatment of cisplatin 1 mM but the cell number of ICs was not affected. In lateral line HCs, the mechanotransducer channel mediated Ca2+ influx and the number of HCs (labeled with S100) were suppressed by 0-96 hpf treatment of 10 μM and 100 μM cisplatin. Acute exposure to 500 μM cisplatin for 30 min also significantly suppressed Ca2+ influx of HCs. Exposure to cisplatin caused both acute and chronic toxicity to the development and function of HCs and ICs.