环孢素肾毒性的体外评价
首发时间:2010-02-09
摘要:细胞体外培养模型可以在药物开发的早期淘汰毒性过大的药物,从而缩短研究周期并降低开发成本。目前常用的细胞体外培养模型是单层贴壁培养,但其往往不能准确反映药物在体内的毒性。因此,本文将凝胶包埋培养技术用于原代肾小管上皮细胞的体外培养。结果表明,相对于单层贴壁培养,凝胶包埋培养的肾小管上皮细胞较好地保持了细胞的碱性磷酸酶和多药耐药性蛋白2(Mrp2)的活性。另一方面,将环孢素作为模型药物考察凝胶包埋肾小管上皮细胞用于肾毒性评价的可行性,通过与单层贴壁培养模型的对比,发现凝胶包埋培养模型能更敏感地反映环孢素在体内导致的肾毒性和过氧化应力的情况。
关键词: 生物化学工程 肾毒性 凝胶包埋培养 单层贴壁培养 环孢素
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Evaluating the nephrotoxicity of cyclosporin A in vitro
Abstract:During the drug development, the application of cell culture model for drug toxicity screening could facilitate to eliminate drug candidates with high toxicity, thus shorten the development phase and reduce the cost. To date, the monolayer culture model is the most commonly used in vitro model. But the toxicity of drugs in vivo could not always be accurately reflected. Therefore, this study employed the gel entrapment model for renal tubular epithelial cell culture. The results showed that the activities of alkaline phosphatase and multidrug resistant protein 2 (Mrp2) were better maintained in gel entrapment model, compared to monolayer culture. On the other hand, cyclosporin A was employed as a model drug to evaluate the feasibility of gel entrapped renal tubular epithelial cells in drug nephrotoxicity screening. Comapred with the toxic response and oxidative stress in monolayer culture model, gel entrapment culture model could sensitively reflect the nephrotoxicity induced by cyclosporin A in vivo.
Keywords: biological engineering nephrotoxicity gel entrapment culture monolayer culture cyclosporine A
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