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目的研究抗钠-钙交换体α-2(815-839)抗体对Langendorff离体灌流大鼠心功能的影响并分析其机制。方法以人工合成的α-2(815-839)作为抗原肽段免疫大鼠获得并纯化抗体,利用Langendorff离体灌流系统研究其对大鼠心功能的影响。结果免疫后大鼠体内抗α-2(815-839)抗血清滴度明显升高,纯化后抗体浓度为1.2 mg/ml,在PAGE电泳时仅有一条带出现,分子量与IgG标准品相一致。在浓度为10,20和40 nmol/L时,该抗体可剂量依赖性地升高离体灌流大鼠心脏左室发展压(LVDP)、左室压最大上升速率(+dP/dtmax)和左室压最大下降速率(-dP/dtmax),且这一效应可被NCX特异性阻断剂KB-R7943阻断。高钙溶液灌流可使离体心脏LVDP和+dP/dtmax增大,而使-dP/dtmax明显降低。结论抗α-2(815-839)抗体通过激动心肌钠-钙交换体和L型钙通道不仅可以增强心肌的收缩力和加快心肌收缩的速度,而且还可促进心肌的舒张,为研发防治心力衰竭新型药物提供了实验依据。
Objective To investigate the effects of anti-sodium-calcium exchanger α-2 (815-839) on cardiac function in isolated perfused Langendorff rats and its mechanism. Methods The artificial anti-α-2 (815-839) antigen was used to immunize rats to obtain and purify the antibody. The Langendorff perfusion system was used to study the influence of the antibody on cardiac function in rats. Results The titer of anti-α-2 (815-839) antiserum was significantly increased after immunization in rats. After purification, the antibody titer was 1.2 mg / ml. Only one band appeared on PAGE electrophoresis. The molecular weight was consistent with IgG standard . At 10, 20 and 40 nmol / L, the antibody could increase the left ventricular ejection fraction (LVDP), the maximum rate of left ventricular pressure (+ dP / dtmax) and left The maximum rate of decline in ventricular pressure (-dP / dtmax), and this effect can be NCX-specific blocking agent KB-R7943 block. High perfusion of calcium solution can increase the isolated heart LVDP and + dP / dtmax, while the-dP / dtmax decreased significantly. Conclusions Anti-α-2 (815-839) antibody not only enhances cardiac contractility and myocardial contractile speed by activating cardiac sodium-calcium exchanger and L-type calcium channels, but also promotes myocardial relaxation, The failure of new drugs provides experimental evidence.