阿托伐他汀对异丙肾上腺素诱导的心力衰竭小鼠胞浆内钙火花影响的研究  

The effect of atorvastatin on cytoplasmic calcium sparks in isoproterenol-induced heart failure mice model

作　　者：张鹤萍[1] 钱海超[1] 熊杰[2] 罗大力[2] 吴永全[1] 

机构地区：[1]首都医科大学附属北京友谊医院心内科,北京100050 [2]首都医科大学化学生物学与药学院,北京100069

出　　处：《临床和实验医学杂志》2017年第16期1569-1574,共6页Journal of Clinical and Experimental Medicine

基　　金：首都医科大学基础-临床科研合作基金(编号:10JL28)

摘　　要：目的研究阿托伐他汀对心力衰竭(心衰)小鼠心功能的影响,探索阿托伐他汀介导的心脏保护作用的潜在机制。方法将60只C57 BL小鼠用随机数字表随机分为三组:心衰模型组(HF组),心衰基础上给予阿托伐他汀治疗组(ATO组),正常对照组(WT组)。小鼠心衰模型通过应用微渗泵每天给予200 mg/(kg·d)的异丙肾上腺素建立,HF组基础上同时给予20 mg/(kg·d)阿托伐他汀治疗制备ATO组。应用超声心动图评估模型建立成功与否及不同组别心功能情况。每组动物的心室肌细胞分离及应用荧光染料Fluo4/AM标记后即可进行共聚焦显微镜扫描,观察指标为钙火花及钙瞬变。结果 ATO组在给药1周后与HF组相比明显改善了小鼠心功能(ejection fraction=51%vs.39%,P<0.001),共聚焦扫描发现WT组和ATO组之间自发钙火花的发生频率(Ca SF)无统计学差异[5.20±0.91 vs.6.06±0.53 sparks/(100μm·s)],P=0.336),但此两组均表现出明显低于HF组的Ca SF(HF组12.41±1.46,WT组5.20±0.91;P=0.002,12.41±1.46 for HF vs.6.06±0.53 for ATO;P=0.001)。在钙火花的描述参数方面,半最大全宽度(FWHM)和半最大全时程(FDHM)在ATO组较HF组都有所下降。结论阿托伐他汀能改善心衰小鼠的心功能,其潜在机制可能与部分重塑心衰细胞的钙火花有关。Objective To explore the effect of atorvastatin on heart failure mice model and to study the underlying mechanism of atorvastatin-mediated myocardium protection. Methods Sixty C57 BL mice were randomly divided into three groups： heart failure model group（ HF group）,heart failure plus atorvastatin treatment group（ ATO group） and control group（ WT group）. The heart failure mice models were established by receiving isoproterenol 200 mg/kg/day for 1 week,with the help of mini-osmotic pumps. Cardiac function was assessed by using high frequency echocardiography. Ca2＋signaling was monitored in freshly isolated mouse ventricular myocytes by Fluo4/AM. Results In the atorvastatin group,atorvastatin treatment significantly prevented the decrease of cardiac function in isoproterenol exposed mice（ ejection fraction = 51%vs. 39%,P 〈 0. 001） after 1 week. ATO treatment mice showed less calcium sparks compared with that of HF group（ 12. 41 ± 1. 46 for HF vs.5. 20 ± 0. 91 for WT; P = 0. 002; 12. 41 ± 1. 46 for HF vs. 6. 06 ± 0. 53 for ATO; P = 0. 001）,and the FWHM and FDHM had been remolding to a better degree by atorvastatin. Conclusion This experimentation in mice model suggests that atorvastatin treatment may remold part of the calcium remodling in isoproterenol induced heart failure in mice to improve the cardiac function.

关 键 词：小鼠 心力衰竭 异丙肾上腺素 阿托伐他汀 钙火花 

分 类 号：R541.6[医药卫生—心血管疾病]