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目的:探讨阿霉素诱导大鼠线粒体DNA 4834 bp缺失突变动物模型中,内耳、肾脏和骨骼肌组织中该缺失突变的不同发生情况及可能机制。方法:Wistar大鼠28只,随机分为实验组(18只)和空白对照组(10只)。实验组给予阿霉素1 mg/kg,腹腔注射,每周2次,共3个月;空白对照组给予生理盐水。采用巢式PCR技术,检测内耳、肾脏和骨骼肌组织中线粒体DNA 4834 bp缺失突变的发生情况。PCR产物直接测序。结果:实验组和对照组分别有2只动物死亡。实验组大鼠内耳、肾脏和骨骼肌组织的线粒体DNA 4834 bp缺失突变发生率分别为68.75%(11/16),75.00%(12/16)和100.00%(16/16),经统计学检验(Fisher精确概率检验),内耳组织和肾脏组织间突变发生率差异无统计学意义(P>0.05);内耳组织和骨骼肌组织间差异有统计学意义(P<0.05)。对照组大鼠的3种组织均未检测到该缺失突变。结论:阿霉素可以诱发大鼠线粒体DNA 4834 bp缺失突变,并且在大鼠内耳和骨骼肌组织中,线粒体DNA 4834 bp缺失突变发生率显著不同,提示该突变存在组织特异性。
Objective: To investigate the different occurrence and possible mechanism of adriamycin-induced mitochondrial 4848 bp deletion mutation in the inner ear, kidney and skeletal muscle. Methods: 28 Wistar rats were randomly divided into experimental group (n = 18) and blank control group (n = 10). The experimental group was given adriamycin 1 mg / kg, intraperitoneal injection twice a week for 3 months; the blank control group was given normal saline. Nested PCR was used to detect the occurrence of mitochondrial DNA 4834 bp deletion in the inner ear, kidney and skeletal muscle. PCR products were sequenced directly. Results: Two animals died in the experimental group and the control group respectively. The 4834 bp deletion mutation in the inner ear, kidney and skeletal muscle of experimental group was 68.75% (11/16), 75.00% (12/16) and 100.00% (16/16), respectively. The statistical analysis (Fisher exact test), there was no significant difference in the incidence of the mutation between inner ear tissue and kidney tissue (P> 0.05). There was significant difference between inner ear tissue and skeletal muscle (P <0.05). None of the three tissues in the control group detected this deletion mutation. CONCLUSION: Doxorubicin can induce a 4834 bp deletion mutation in mitochondrial DNA in rats, and the incidence of 4834 bp deletion mutation in the inner ear and skeletal muscle of rats is significantly different, suggesting that the mutation has tissue specificity.