辛伐他汀对病毒性心肌炎小鼠心肌细胞L-型钙通道mRNA表达的影响  

Effect of simvastatin on gene expression of L-type calcium channels in mouse myocardium with myocarditis caused by coxsackievirus B3

作　　者：窦忠霞[1] 王举[2] 魏征人[3] 孙景辉[1] 

机构地区：[1]吉林大学第一医院小儿心血管科,吉林长春130021 [2]吉林大学第一医院结直肠肛门外科,吉林长春130021 [3]吉林大学基础医学院药理学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2009年第1期78-81,195,共5页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科技发展计划项目资助课题(200705157)

摘　　要：目的:研究辛伐他汀对柯萨奇B3病毒(CVB3)感染BALB/c小鼠后心肌细胞L-型钙通道(LCCs)mRNA表达的影响,探讨辛伐他汀对病毒性心肌炎的治疗作用。方法:应用CVB3感染BALB/c小鼠制作病毒性心肌炎模型,辛伐他汀混悬液灌胃,按辛伐他汀剂量分为10 mg.kg-1组、30 mg.kg-1组及90 mg.kg-1组,并设正常对照组及病毒感染对照组,行心肌病理观察,采用半定量逆转录-聚合酶链式反应(RT-PCR)检测正常对照组、病毒感染组及辛伐他汀组心肌细胞LCCsα1亚单位mRNA表达量。结果:病毒感染组小鼠心肌组织有局灶性或弥漫性以单核细胞为主的炎性细胞浸润,重者可见大片状心肌细胞坏死;辛伐他汀组心肌组织炎症细胞浸润及坏死灶明显减轻;正常对照组和病毒模型组心肌LCCsα1亚单位的mRNA表达量分别为0.06±0.01和1.37±0.32,二者比较差异有显著性(P<0.05);辛伐他汀10 mg.kg-1、30 mg.kg-1及90 mg.kg-1组LCCsα1亚单位的mRNA表达量分别为1.14±0.22、0.17±0.04和0.11±0.02,与病毒模型组比较差异有显著性(P<0.05),其中以中、高剂量组下降最明显。结论:辛伐他汀可减轻病毒性心肌炎的病理损害,并以剂量依赖的方式抑制心肌细胞LCCsα1亚单位的mRNA表达,发挥心肌保护功能,对病毒性心肌炎有一定的治疗作用。Objective To investigate the effect of simvastatin on gene expression of L-type calcium channels （LCCs） of myocardial ceils in BALB/c mice infected by coxsackievirus B3 （CVB3） so as to study the therapeutic effect of simvastatin on viral myocarditis. Methods Sixty male BALB/c mice were divided into five groups randomly （n= 12）. Mice in viral control group and three groups of oral administration of simvastatin （10, 30 and 90 mg · kg^-1） were inoculated intrapritoneally with 0.2 mL of CVB3 （Nancy strain）. Mice in normal control group were inoculated intrapritoneally with 0.2 mL Eagle＇s solution. The heart samples of all the mice were obtained for hispathological study and detection of myocardial LCCs alphal subunits mRNA expression by semi-quantitative reverse transcription- polymerase chain reaction （RT-PCR）. Results In viral control group, the mononuelear inflamematory infiltrate was focal or diffuse in myocardium of mice, severe hearts revealed a large area of myocardial necrosis. The degree of inflammatory cell infiltrate and area of necrosis were significantly less in simvastatin groups as compared with viral control group. The myocardial LCCs alphal suhunits mRNA expression by semi - quantitative RT-PCR in normal control group was much lower than that in viral control group （0. 06±0. 01 vs 1.37± 0.32, P〈0. 05）; the expression levels of myocardial LCCs alphal subunits mRNA in simvastatin （10, 30 and 90 mg · kg^-1 ） groups were 1.14 ± 0. 22, 0. 17± 0. 04 and 0. 11 ± 0. 02, respectively, and they were lower than that in viral control group （P〈0.05）; In simvastatin （30 and 90 mg · kg^-1） groups, the myocardial LCCs alpha1 subunits mRNA expressions were significantly decreased （P〈0. 05） . Conclusion Simvastatin could reduce the grade of myocardial damage and block virus-induced LCCs alpha1 subunit gene expression in a dose-dependent manner, which might exert a protective effect in myoearditis mice infected by CVB3.

关 键 词：辛伐他汀 心肌炎 L-型钙通道 

分 类 号：R331.31[医药卫生—人体生理学] R-332[医药卫生—基础医学]