中文摘要：

目的用大鼠模型评估齐多夫定（AZT）及阿德福韦酯（ADV）对线粒体的毒性损伤。方法SD大鼠随机分为AZT、ADV和空白对照三组，连续灌胃给药28d，检测大鼠肝、肾、骨骼肌、心肌线粒体的细胞色素c氧化酶活性、细胞色素b基因含量，及用电子显微镜观察各组织线粒体超微病理结构的改变隋况。对数据进行方差分析或非参数检验的Kruskal-wallis检验。结果AZT组大鼠细胞色素c氧化酶活性（单位为U／mg）在肝、肾、心肌和骨骼肌分别为9.44±3．09、4．42±1．53、32．74±5．52、33．75±8．74，低于空白对照组的17．8±12．38、14．45±13．75、24．74±20．59、40．04±2．49，也较ADV组低，但三组间的差异均无统计学意义（肝脏：H=3．08，P=0．21，肾脏：H=3．44，P=0．18；骨骼肌：H=1．61，P=0．45；心肌：H=2．52，P=0．28）。AZT组大鼠线粒体细胞色素b基因含量在肝脏、心肌分别为0．61±0．95、0．15±0．13，ADV组分别为0．52±0．68、0．17±0．08，相比空白对照组明显减少，但差异无统计学意义（肝脏：H=3．398，P=0．18，心肌：H=0．33，P=0．85）。AZT组的肝、肾、骨骼肌和心肌都出现明显的线粒体损伤改变。结论连续给药28d后，AZT可造成明显的线粒体损伤，而ADV仅导致线粒体细胞色素b基因含量偏低。

英文摘要：

Objective To explore the mitochondrial toxicities induced by zidovudine （AZT） and adefovir dipivoxil （ADV） antiviral drugs using a rat model system. Methods Twelve healthy Sprague- Dawley rats were randomly divided into three equal groups and treated by oral gavage with zidovudine （125 mg/kg/day）, adefovir （40 mg/kg/day）, or saline （equal volume） for 28 days. The rats＇ body weights were measured once a week, and blood was collected every two weeks for blood and biochemical tests. All animals were sacrificed at the end of treatment, and liver, kidney, skeletal muscle, and cardiac muscle were collected by necropsy. Mitochondria were isolated from the respective tissue samples, and the activities of respiratory chain complexes were measured. DNA was purified from each sample and the mitochondrial DNA （mtDNA） content was monitored by quantitative real time PCR. Mitochondrial morphology was analyzed under electron microscope. Results No significant adverse effects, including body weight loss, abnormal blood or biochemistry, were observed in rats treated with AZT or ADV. The activities of mitochondrial cytochrome c oxidase in liver and cardiac muscle were slightly decreaseA in rats treated with AZT （livcr： 9.44 ± 3.09 vs. 17.8 ± 12.38, P = 0.21; cardiac muscle： 32.74 ± 5.52 vs. 24.74 ± 20.59,P = 0.28; kidney： 4.42 ± 1.53 vs. 14.45 ± 13.75,P = 0.18; skeletal muscle： 33.75 ± 8.74 vs. 40.04 ± 2.49, P = 0.45）. The mtDNA content was significantly decreased in cardiac muscle of AZT-treated rats （cardiac muscle： 0.15 ± 0.13 vs. 0.32 ± 0.42, P = 0.85）. The morphology of mitochondria in liver, kidney, skeletal muscle, and cardiac muscle was significantly altered in the AZT-treated rats and included disappearance of the outer membrane, severely damaged structure, and swollen or completely absent cristae. No obvious effects were noted in the ADV- or saline-treated rats. Conclusion Significant adverse effects related to mitochondrial toxicity were observed in rats treated with