核苷类似物对小鼠肝细胞线粒体DNA ND1和ND4的影响

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Abstract Objective To investigate whether long-term use of nucleoside analogues (NAs) can lead to damage of DNA (mtDNA) ND1 and ND4 regions in liver mitochondria of mice. Methods According to the simple random method, twenty-five 7-weeks-old female Balb/c mice were divided into 5 groups, with 5 cases in each group. The control group received double-distilled water by intraperitoneal injection 5 days per week for 3 months. The each test group was respectively given D4T 50 mg/kg, AZT 100 mg/kg,3TC 50 mg/kg,or DDI 50 mg/kg by intraperitoneal injection per day,5 days per week for 3 months. Single liver cell was captured from mouse liver tissues by laser capture microdissection. The products of mtDNA ND1 and ND4 region PCR amplicons were cloned and sequenced in mice liver cells. Results The mean distance to the reference sequence of mtDNA ND4 in the captured hepatocytes of AZT, D4T and 3TC groups were longer than that in the control group, the differences were statistically significant (P < 0.01). The mean mtDNA ND4 dN of the captured hepatocytes in the AZT group was higher than that in the control group, the difference was statistically significant (P < 0.05). The mean distance to the reference sequence of mtDNA ND1 in the captured hepatocytes of AZT and 3TC groups were longer than that in the control group, the differences were statistically significant(P < 0.01). The mean mtDNA ND1 dS of the liver tissue in the DDI group was higher than that in the control group, the difference was statistically significant (P < 0.05). The mean mtDNA ND1 dS of AZT and 3TC groups were higher than that in the control group, the differences were statistically significant(P < 0.05). Conclusion Long-term exposure to nucleoside analogue can result in mtDNA ND1 and ND4 regions lesion in mouse hepatocytes.

Key words： mtDNA ND1 mtDNA ND4 Laser capture microdissection Mitochondrial toxicity Nucleoside analogue

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	ZHANG Wei1* QIAO Luxin1
	2* DING Wei1 CHEN Dexi1
	2 ZHANG Yulin1▲

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ZHANG Wei1* QIAO Luxin1,2* DING Wei1 CHEN Dexi1,2 ZHANG Yulin1▲. Mitochondrial DNA ND1 and ND4 mutation in liver and captured hepatocytes of mice after long-term nucleoside analogues exposure[J]. 中国医药导报, 2018, 15(21): 8-13.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2018/V15/I21/8

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