降钙素基因相关肽对高脂复合缺氧／复氧诱导乳鼠心肌细胞凋亡的影响

背景：前期研究表明，结扎冠状动脉可诱发大鼠传入神经纤维末梢逆向释放降钙素基因相关肽，提示降钙素基因相关肽参与了急性心肌缺血的病理生理过程。目的：观察降钙素基因相关肽对氧化低密度脂蛋白孵育缺氧/复氧诱导的乳鼠心肌细胞凋亡的影响。方法：20孔原代培养的乳鼠心肌细胞随机分为5组：正常对照组、氧化低密度脂蛋白组、氧化低密度脂蛋白＋缺氧/复氧组、降钙素基因相关肽组和CGRP 8-37组。后4组均用氧化低密度脂蛋白孵育24 h，再建立心肌细胞缺氧/复氧模型；降钙素基因相关肽组在缺氧/复氧前30 min加入10-8 mol/L 降钙素基因相关肽，CGRP 8-37组在给予降钙素基因相关肽前30 min加入10-7 mol/L的降钙素基因相关肽1受体的竞争性拮抗剂CGRP 8-37。采用流式细胞仪检测心肌细胞凋亡率并测定caspase-3活性。结果与结论：降钙素基因相关肽能明显抑制氧化低密度脂蛋白和缺氧/复氧处理的乳鼠心肌细胞caspase-3的激活，从而阻止凋亡的发生，并且该作用能被降钙素基因相关肽1受体的竞争性拮抗剂CGRP 8-37部分逆转，说明降钙素基因相关肽通过与降钙素基因相关肽1受体结合产生抗凋亡效应，进而抑制心肌细胞凋亡，对氧化低密度脂蛋白孵育乳鼠心肌细胞的缺氧/复氧损伤具有保护作用。

Calcitonin gene-related peptide affects cardiomyocyte apoptosis of neonatal rats induced by oxidized low-density lipoprotein and hypoxia/reoxygenation

BACKGROUND：Previous studies have shown that calcitonin gene-related peptide can be released from cardiac sensory afferent terminals fol owing coronary artery occlusion in rats, indicating the involvement of calcitonin gene-related peptide during pathological process of acute myocardial ischemia.OBJECTIVE：To investigate the effect of calcitonin gene-related peptide on neonatal rat cardiomyocytes apoptosis induced by oxidized low-density lipoprotein and hypoxia/reoxygenation.METHODS：Twenty wel s of primary cultured neonatal rat myocardial cel s were randomly divided into five groups：normal control group, oxidized low-density lipoprotein group, oxidized low-density lipoprotein hypoxia/reoxygenation group, calcitonin gene-related peptide group and calcitonin gene-related peptide 8-37 group. The cel s in the last four groups were incubated with oxidized low-density lipoprotein for 24 hours before establishing the myocardial hypoxia/reoxygenation model. At 30 minutes prior to hypoxia/reoxygenation, 10-8 mol/L calcitonin gene-related peptide were added into the culture fluid in calcitonin gene-related peptide group;10-7 mol/L competitive antagonist calcitonin gene-related peptide 8-37 of calcitonin gene-related peptide-1 receptor were added at 30 minutes before calcitonin gene-related peptide administration in calcitonin gene-related peptide 8-37 group. Myocardial apoptotic rate and caspase-3 activity were detected respectively.RESULTS AND CONCLUSION：Calcitonin gene-related peptide could significantly attenuate apoptosis of＆amp;nbsp;neonatal rat myocardial cel s through inhibiting the caspase-3 activation induced by oxidized low-density lipoprotein and hypoxia/reoxygenation. And this effect could be partial y reversed by competitive antagonist calcitonin gene-related peptide 8-37 of calcitonin gene-related peptide 1 receptor, indicating that calcitonin gene-related peptide has anti-apoptotic effect in combination with the calcitonin gene-related peptide 1 receptor to inhibit cardiomyocyte apoptosis in neonatal rats induced by oxidized low-density lipoprotein and hypoxia/reoxygenation.