阿托伐他汀对病毒性心肌炎小鼠心脏的影响

Effects of atorvastatin on the improvement of heart function in mice with viral myocarditis

目的探讨阿托伐他汀（atorvastatin）对病毒性心肌炎（VMC）小鼠心脏组织及功能的影响。方法4周龄近交系纯种Balb／c小鼠146只随机（随机数字法）分为4组：（1）健康组（n=18）；（2）VMC组（n=60），腹腔接种柯萨奇病毒；（3）对照组（n=18），只给予阿托伐他汀；（4）VMC药物治疗组（n=50），给予腹腔接种柯萨奇病毒，并给以阿托伐他汀连续治疗用药2周。接种病毒后3，7，10，14，21，30d，检测超声心动图、收集血样检测血清cTnI水平，HE染色观察心肌组织炎症浸润程度，电镜观察心肌胶原纤维、心肌细胞及各种细胞器的变化。资料组问比较采用方差分析，post—hoc检验用于比较各组生存间的差异。结果VMC组比VMC药物治疗组的30d累计生存率低（59．2％VS．87．0％），差异具有统计学意义（P=0．008）。VMC药物冶疗组与VMC组比较，在第lO，14，21，30天的心肌病理组织学积分均降低，差异具有统计学意义（P〈0．05）。VMC药物治疗组比VMC组心肌损伤的病灶数量少，心肌线粒体和肌浆网改变也较同期VMC组轻。腹腔注射病毒后第7天与对照组比较，VMC组小鼠出现心功能减低[（69．82±5．12）VS．（89．23±2．01），P〈0．01]。与VMC组比较，VMC药物治疗组EF值明显增高[（78．99±5．23）VS．（69．82±5．12），P〈0．01]；与VMC组比较，VMC药物治疗组的cTnI值明显下降。结论阿托伐他汀改善VMC小鼠生存率，改善组织病理学表现，减少心肌受损程度，提高心脏功能。阿托伐他汀可能是一种潜在的治疗VMC的方法。

Objective To investigate the effects of atorvastatin on the improvement of cardiac function of mice with myocarditis. Methods A total of 146 Balb/c mice were divided into four groups randomly （random number）. The viral myoearditis （VMC） model was made by Coxsakie virus B3 （CVB） injected intra-abdominally. Four groups were normal group （n = 18）, VMC group （n = 60）, Control group （ n = 18 ） and VMCtreatment group （ n = 50 ）. The mice of control group were treated with atorvastatin without VMC, and the mice of VMC treatment group were with VMC and were given atorvastatin for 2 weeks. Eehocardiograms were used 3, 7, 10, 14, 21, and 30 days after virus inoculation. Blood samples were collected for cardiac troponin-I detection at the same time. Myocardial inflammation was examined by using histochemistry staining. The changes of myocardial collagen fiber, myocardial cells and various organelles were examined by electron microscope. Results Compared with VMC group, the cumulative survival rate of VMC group treatment group was higher （ 87.0% vs 59. 2% ） after treatment with atorvastatin for 30 days （P = 0. 008 ） , and the improvement of pathological features after treatment with atorvastatin was found 10, 14, 21 and 30 days after the inoculation. Compared with control group, the cardiac function was decreased in the CVB infected mice 7 days after virus challenge [ （69.82 ±5.12） vs （89. 23±2.01）, P 〈0. 01 ] and compared with VMC group, the EF values of VMC treatment group were significantly higher 7, 14, 21 and 30 days after virus inoculation. The differences in cTnI values between VMC group and CVB treatment group were statistically significant 7, 10, 14 and 21 days after virus challenge. Conclusions These results demonstrate that atorvastatin improves survival rates and the histological features in CVB3m-induced myocarditis. It can improve the heart function of CVB infected mice. Atorvastatin could be a treatment of choice for VMC.