采用HepG2和HK-2细胞模型评价富马酸泰诺福韦双特戊酯的线粒体毒性  

Research on the mitochondrial toxicity of tenofovir dipivoxil fumarate on HepG2 and HK-2 cells

作　　者：杨遵远 龚立 冯兴磊 曾文 

机构地区：[1]中国医药集团公司四川抗菌素工业研究所,中国医药集团安全性评价研究中心,成都610052

出　　处：《中国新药杂志》2013年第5期513-519,共7页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2011ZX09301-001);国家自然科学基金(3090131)

摘　　要：目的:评价富马酸泰诺福韦双特戊酯的线粒体毒性,为临床试验剂量设计和合理用药提供参考。方法:测定HepG2和HK-2细胞增殖抑制率,培养液上清乳酸含量,线粒体呼吸链复合体活性,mtDNA含量和线粒体结构变化,用已上市阳性药物验证,综合评价受试物线粒体毒性。结果:与对照组比,高剂量组对两种细胞均具有明显线粒体毒性,中剂量组毒性较弱,低剂量组无明显毒性。结论:富马酸泰诺福韦双特戊酯25μg.mL-1对机体肝组织的潜在线粒体毒性较弱;富马酸泰诺福韦双特戊酯40μg.mL-1对机体肾组织的潜在线粒体毒性较弱。Objective： To evaluate the potential mitochondrial toxicity of tenofovir dipivoxil fumarate and provide evidence for clinical dose design and drug use. Methods： The cell inhibition rate, lactate content in culture solution, mitoehondrial mtDNA content, and activities of mitochondrial respiratory chain complexes of HepG2 and HK-2 cells were measured. The morphology and strueture of mitochondria were observed under transmission e- lectron microscope. Results： Compared with the control group, mitoehondrial toxicity were obvious on both kinds of cells in the high-dose group, and less in the middle-dose group, and no significant toxicity was observed in the low- dose group. Conclusion ： The potential mitoehondrial toxicity of tenofovir dipivoxil fumarate to liver tissues and kid- ney tissues are relatively weak at the concentrations of 25μg·mL^-1and 40μg·mL^-1 respectively.

关 键 词：富马酸泰诺福韦双特戊酯 HEPG2细胞 HK-2细胞 线粒体毒性 实时定量PCR 

分 类 号：R992[医药卫生—毒理学]