骨髓间充质干细胞对病毒性心肌炎小鼠的干预作用

Intervention effects of bone marrow mesenchymal stem cells on viral myocarditis in mice

目的探讨骨髓间充质干细胞(BMSCs)对小鼠病毒性肌炎的作用。方法 4周龄BALB/C雄性小鼠随机分为,正常对照组、心肌炎组、心肌炎不同阶段(3天、2周)BMSCs干预组,腹腔注射柯萨奇病毒B3建立病毒性心肌炎小鼠模型,干预组分别于注射病毒后3天、2周尾静脉注射小鼠BMSCs,4周后行心脏超声检查,光镜观察并计算心肌组织病理积分及胶原容积分数(CVF),q RT-PCR法检测心肌组织匀浆胶原纤维I(col1α1)和胶原纤维III(col3α1)m RNA表达。结果与正常对照组相比,心肌炎组左室前后壁变薄,左室收缩期末期内径和容积增大,左室射血分数(LVEF)及短轴缩短率(FS)降低,差异均有统计学意义(P均<0.05);干预组各亚组LVEF及FS较心肌炎组均有改善,其中心肌炎2周时干预组改善更明显,差异均有统计学意义(P均<0.05)。光镜下,心肌炎组心肌组织CVF较正常对照组增高,干预组CVF较心肌炎组降低,其中心肌炎2周干预组CVF较心肌炎3天干预组更低,差异均有统计学意义(P均<0.05)。与正常对照组相比,心肌炎组col1α1和col3α1 m RNA表达均升高,干预组col1α1和col3α1 m RNA表达较心肌炎组降低,差异均有统计学意义(P均<0.05)。结论 BMSCs可减少病毒性肌炎小鼠心脏纤维化程度及改善心功能,且病毒感染2周时干预效果更佳。

Objective To explore the effects of bone marrow mesenchymal stem cells(BMSCs)on viral myositis in mice.Methods Four-week-old BALB/C male mice were randomly divided into normal control group,myocarditis group,and BMSCs intervention group at different stages(3days and2weeks).The mouse model of viral myocarditis was established by intraperitoneal injection of Coxsackie virus B3.The mice in the intervention group were injected with BMSCs in the tail vein at3days and2nd week after the injection of the virus.Four weeks later,echocardiography was performed,and the pathological integral and collagen volume fraction(CVF)were observed and calculated by light microscopy.The qRT-PCR method was used to detect the mRNA expression of homogenates collagen I(col1α1)and collagen fiber III(col3α1)in myocardial tissue.Results Compared with the normal control group,the left anterior and posterior wall became thinner,the diameter and volume of the left ventricle at end systolic period was increased;left ventricular ejection fraction(LVEF)and short axis shortening rate(FS)decreased in the myocarditis group.The differences were statistically significant(P all<0.05).The LVEF and FS in each subgroup of the intervention group were better than those of the myocarditis group,and the improvement in the intervention group was more obvious at the2nd week after the treatment of the myocarditis.The differences were significant(P all<0.05).Light microscope showed that myocardial CVF in myocarditis group was higher than in normal control group,and CVF in intervention group was reduced compared with myocarditis group and CVF in the2nd week intervention group was lower than that in the3day intervention group.The differences were significant(P all<0.05).Compared with the control group,the mRNA expressions of col1α1and col3α1in the myocarditis group were increased,and they were lower in the intervention group than in the myocarditis group,and the differences were significant(P all<0.05).Conclusions BMSCs can reduce the degree of cardiac fibrosis and improve cardiac function in mice with viral myositis,and the intervention effect is better when the virus is infected in the2nd week.