摘要
OBJECTIVE: To assess complement-mediated myocardial injury on isolated guinea pig working hearts and cardioprotective effects of CD59. METHODS: Using a modified Langendorff apparatus, isolated guinea-pig working hearts were perfused with a modified Krebs Henseleit buffer containing 3% heat-inactivated human plasma and zymosan (IPZ) (control) (n = 10), 3% normal human plasma and zymosan (NPZ) (n = 10), or 3% normal human plasma and zymosan and 1.5 microg/ml CD59 (NPZC) (n = 10), respectively. Epicardial electrocardiogram (ECG), cardiac output (CO), coronary arterial flow (CF), maximum left ventricular developed pressure (LVP(max)), maximum left ventricular developed pressure increase rate (+ dp/dt(max)), maximum left ventricular developed pressure decrease rate (- dp/dt(max)) and heart rate (HR) were recorded at 0, 15, 30, 45 and 60 min of treatment. After the experiment, immunohistochemical examination was performed to detect the presence of C3a or C5b-9 in the myocardium of the isolated hearts. RESULTS: Compared the IPZ group, hearts treated with NPZ showed a slight depression on ST segments of epicardial ECG at 15 min, a significant elevation between 30 min to 60 min, a decrease in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max), and an increase in HR at 15 min. The observed alterations in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max) remained decreased, while the HR remained increased until the end of the protocol. The all above parameters of hearts treated with NPZC were similar to the control group (IPZ) at any given time. Immunohistochemical examination showed positive signals of C3a and C5b-9 in the myocardium of hearts treated with NPZ. C3a was positive in NPZC, and C3a and C5b-9 were negative in IPZ. CONCLUSIONS: Activated human complements directly damage isolated guinea pig working hearts, and CD59 offers a significant protection against the injuries.
目的 一系列的研究表明补体激活在心肌损伤中起重要作用。然而 ,补体激活对心肌的直接损伤作用以及补体介导损伤的机制尚不清楚。本研究评价补体介导的豚鼠离体工作心脏损伤以及CD5 9对补体介导心肌损伤的保护作用。方法 使用改良的Langendorff灌注装置 ,以Krebs Henseleit灌注液灌注离体豚鼠工作心脏 ,然后分别在灌注液中加入 3%灭活人血浆 +酵母多糖 (IPZ组 ,n =10 ) ,3%人血浆 +酵母多糖 (NPZ组 ,n =10 )和CD5 9(1 5 μg/ml) + 3%正常人血浆 +酵母多糖 (NPZC组 ,n =10 ) ,记录各组处理前和处理后 15、30、4 5和 6 0分钟的心率 (HR)、心输出量(CO)、冠脉流量 (CF)、左心室最大内压 (LVPmax)、左室内压最大上升和下降速度 (±dp/dtmax)和心外膜心电图 ,并在实验结束时取左心室心肌组织进行免疫组化检查 ,观察有无C3a或C5b 9在心肌组织沉积。结果IPZ组处理后心外膜心电图和血流动力学指标均无明显变化。NPZ组工作心脏在处理后 15分钟出现心外膜心电图ST段轻度下移 ,30 - 6 0分钟之间ST段变为明显抬高 ;处理后 15 - 6 0分钟HR增加 ,CF、CO、LVPmax、+dp/dtmax和 -dp/dtmax下降 ,这些变化以处理后 4 5分钟最明显。NPZC组上述指标处理前后与IPZ组比较无显著性差异。免疫组化检查 :IPZ组未见C3a或C5b
基金
theScientificResearchFoundationoftheMinistryofHealth ,China (No .96 1115 )
