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Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis 被引量:11
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作者 孟晓慧 汪翼 +7 位作者 庄建新 韩秀珍 陈瑶 靳有鹏 王玉林 于永慧 james p.spires 宋国杰 《Chinese Medical Journal》 SCIE CAS CSCD 2004年第8期1195-1199,共5页
Background Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart The purpose of this study was to investigate the dynamic ch... Background Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM KH*2/5DMethods Sixty-five six-week-old male DBA/2 mice were divided into two groups Mice in the infected group (n=50) were inoculated intraperitoneally with 0 14 ml of Coxsackievirus B 3 (CVB 3, Nancy strain) Control mice (n=15) were inoculated intraperitoneally with 0 14 ml of Eagle’s medium Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation MMP activity was measured on an SDS-PAGE substrate gel embedded with type Ⅰ gelatin (zymography) Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0 01 ml/g-0 015 ml/g) Cardiac systolic function indices, such as peak velocity of the aorta (V p), flow velocity integral of the aorta (V i), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope The amount of myocardial collagen was measured by means of hydroxyproline quantification Results In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 ( P <0 01) On day 10, cardiac systolic function indices (EF, FS, V p, and V i) were all significantly lower compared both to other stages following viral inoculation and to the control group ( P <0 05) In the acute stage, the amount of myocardial collagen in mice with VM was not significantly different from normal control mice ( P >0 05) However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores ( r =0 801,0 821, P <0 01) and negatively correlated with V p ( r =-0 649, -0 683, P <0 01) and V i ( r =-0 711, -0 755, P <0 01) However, V p negatively correlated with myocardial histopathological scores ( r =-0 756, P <0 01) Conclusions In mice with VM, the activities of myocardial MMP-2 and MMP-9 increase significantly during the acute stage, and the total quantity of myocardial collagen increases by the time of recovery These changes are associated with myocardial interstition remodeling and cardiac dysfunction MMP activity is an important reference marker for myocardial pathological lesions and can be used to evaluate the severity of myocardial interstitial damage and cardiac dysfunction 展开更多
关键词 matrix metalloproteinase viral myocarditis cardiac function REMODELING
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