病毒性心肌炎小鼠心肌细胞线粒体DNA缺失的定量分析

Quantitive analysis of mitochondrial DNA deletion in mice with viral myocarditis

目的:探讨线粒体DNA(mtDNA)缺失在病毒性心肌炎(VMC)发病机制中的作用。方法:50只BALB/c小鼠随机分为2组,实验组(40只)腹腔注射内含CVB3(TCID50=108)的Eagle液制备VMC小鼠模型,另10只为对照组。分别于病毒感染后第3、11和24d行在体心功能和心肌细胞mtDNA3867缺失率测定,并用Spearman法对mtDNA3867缺失率及心功能测值行相关分析。结果:实验组小鼠病毒感染后第3d心肌细胞mtDNA3867缺失率比对照组高8.3倍[(0.01970±0.00118)%vs(0.00211±0.00032)%,P<0.05],同时可见其-dp/dtmax亦显著高于对照组(P<0.05);病毒感染后第11d时,mtDNA3867缺失率比对照组高14.6倍[(0.03292±0.00308)%vs(0.00211±0.00032)%,P<0.05],心脏的收缩(LVPSP、+dp/dtmax)和舒张功能(-dp/dtmax)亦有更显著损伤(均P<0.05);病毒感染后第24d时,mtDNA3867缺失率仍显著高于对照组,比后者高11.5倍,其心功能亦未恢复正常。相关分析显示,mtDNA3867缺失率与LVPSP和+dp/dtmax呈显著负相关,与-dp/dtmax呈显著正相关,相关系数分别为-0.66、-0.79和0.80(均P<0.05)。结论:mtDNA3867缺失可能是VMC发病的病理生理机制之一。

AIM： To elucidate the role of mitochondrial DNA （mtDNA） deletion in the pathogenesis of viral myocarditis in mice. METHODS： 50 BALB/c mice were divided into two groups randomly. 40 were experimental group, each of them was injected 0.1 mL Eagle liquids with CVB3（TCID50 =10^8） intraperitoneally. Another 10 mice were given equal volume Eagle liquids as control group. Cardiac functions in vivo and mtDNA^3867 deletion rate in myocytes were detected separately at the day 3, 11 and 24 after injection. The correlation of mtDNA^3867 deletion rate to cardiac functions was analyzed using Spearman method.RESULTS： At the day 3 after injection, mtDNA^3867 deletion rate in experimental group was 8.3 times higher than that in control group [ （0.01970 ± 0.00118）% vs （0.00211 ± 0.00032）%, P 〈 0.05]. The - dp/dtmax, which reflects cardiac diastolic function, was also damaged （ P 〈0.05）. At the day 11 after injection, mtDNA^3867 deletion rate in experimental group was 14.6 times higher than that in control group [ （0.03292 ± 0.00308） % vs （ 0.00211 ± 0.00032 ） %, P 〈 0.05 ]. Cardiac functions were injured to the most extent in experimental mice as compared with the control group [LVPSP： （79.63 ± 4.69）mmHg vs （99.64 ± 8.21 ） mmHg, P 〈 0.01 ; ＋dp/dtmax： （3088.14 ± 267.86） mmHg/s vs （4903.24 ± 668.36） mmHg/s, P 〈 0.01; - dp/dtmax： （-2463.29 ± 359.92） mmHg/s vs （ -4 172.85 ± 595.97） mmHg/s, P 〈 0.01 ]. At the day 24 after injection, mtDNA^3867 deletion rate and cardiac functions was still significantly higher in CVB3 injected mice. Correlation analysis showed that mtDNA^3867 deletion rate was negative correlation to LVPSP and ＋ dp/dtmax, and positive correlation to - dp/dtmax.Tne correlation coefficient was -0.66, - 0.79 and 0.80, respectively. CONCLUSION： mtDNA^3867 deletion in myocytes might play a role in the pathogenesis of viral myocarditis.