喹诺酮类新药KNT和盐酸莫西沙星肝毒性的比较研究
A comparative study on hepatotoxicity of new quinolones drug KNT and Moxifloxacin hydrochloride
作者：付荣雪;杨遵远;龚立;曾文;
Author：
收稿日期： 年卷（期）页码：2013,28(04):-346-350
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：大鼠原代肝细胞;盐酸莫西沙星;KNT;肝细胞毒性
Key words：
基金项目：国家“十二五”重大新药创制《药物安全性评价关键技术与平台建设》项目资助(2011ZX09301-001);;
成都市科技计划项目(11DXYB141JH-027)
中文摘要
目的采用大鼠原代肝细胞模型评价盐酸莫西沙星(Mox)和喹诺酮类新药KNT的体外肝毒性。方法胶原酶二步灌流法分离制备SD大鼠肝细胞,进行原代培养。Mox和KNT分别设1.6、0.8、0.4、0.2、0.1 mg.mL-1剂量组,同时设溶剂对照组,处理24 h后,检测对比肝细胞活力IC50、AST、胞内LDH泄漏情况、GSH含量变化及两药物不同浓度处理后受损的肝细胞线粒体在电子显微镜下状态的对比。结果 KNT的细胞生长抑制率IC50=0.773 mg.mL-1,显著低于Mox(IC50=1.144 mg.mL-1)。Mox在0.8 mg.mL-1剂量处理24 h后,对大鼠原代肝细胞生长抑制率约69%,培养液上清AST和LDH水平显著升高,肝细胞GSH含量显著降低,电镜观察到肝细胞内绝大部分线粒体肿胀,嵴断裂消失;而Mox在0.4 mg.mL-1剂量下,细胞生长抑制率约8%,AST、LDH和GSH含量无明显改变。经0.8 mg.mL-1KNT处理24 h后,对细胞生长抑制率约9%,培养液上清AST、LDH水平显著低于0.8 mg.mL-1Mox的,与空白对照比有上升趋势,GSH水平也显著上升,电镜观察到肝细胞核轻微固缩,部分线粒体肿胀。在0.4 mg.mL-1KNT剂量下,细胞生长抑制率约1%,AST、LDH和GSH含量无明显改变。结论同剂量下,KNT处理大鼠原代肝细胞24 h后,表现出比Mox肝细胞毒性弱。
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