纳洛酮对大鼠心室肌细胞L-型钙通道的影响王群超-中华麻醉在线.DOC

纳洛酮对大鼠心室肌细胞L-型钙通道的影响 王群超 【摘要 】目的 研究纳洛酮对正常大鼠心室肌细胞L型钙电流(ICa,L)的影响，探讨纳洛酮对心肌收缩力直接作用。方法 采用急性酶解法获得大鼠的单个心室肌细胞，用标准的全细胞膜片钳技术记录钙电流．结果20μg·ml-1和100μg·ml-1的纳络酮分别使钙通道峰值电流幅度从341.19±30.30pA降低至269.62±22.68pA和172.93±21.18pA(n=11,P0.05)。I-V曲线随纳络酮浓度增加逐渐上移，但对激活电位和翻转电位无明显影响。20μg·ml-1和100μg·ml-1的纳络酮抑制率分别为79.02±11.21%和43.28±15.77%（n=5,P0.05）。纳络酮对激活曲线并未产生显著影响。结论 纳洛酮对大鼠心室肌细胞L型钙通道具有直接的抑制作用，其抑制程度具有浓度依赖性。 【关键词】纳洛酮；心室肌细胞；L-型钙电流；膜片钳技术 Effects of naloxone on L-type calcium channels in isolated cardiomyocytes of SD rat Wang Qun-chao.Department of anesthesiology,First Affiliated Hospital of Dalian Medical University,Dalian 116011, China. 【Abstract】 Objective To study the effects of naloxone on L-type calcium channel current in SD rat ventricular myocytes.The aim was to determine the non-opioid effect on direct cardiac muscle contractility.Methods Single ventricular cell of SD rat was obtained by an enzymatic dissociation method,the whole-cell patch clamp recording technique was used to record the change of calcium current .Results Naloxone 20μg·ml-1 and 100μg·ml-1 decreased peak current of ICa,L from 341.19±30.30pA to 269.62±22.68pA and to 172.93±21.18pA(n=11,P0.05).The I-V curve of ICa,L was shifted upwards with higer concentration,but the activation voltage,and the reversal petential of ICa,L were not altered by naloxone.Naloxone 20μg·ml-1 and 100μg·ml-1 reduced the peak current of ICa,L by 79.02±11.21% and 43.28±15.77%（n=5,P0.05）. Naloxone had no significant efect on steady-state activation curve.Conclusions Naloxone inhibites the L-type calcium channels of ventricular myocytes in a concentration-dependent manner. 【Key Words】 Naloxone; Ventricular myocytes;L-type Calcium channel;Patch clamp 纳洛酮是一种合成的羟二氢吗啡酮的N-烯丙基衍生物，是阿片受体特异拮抗剂，而无激动活性，能竞争性阻断并取代阿片样物质与受体的结合，从而解除中枢抑制作用。临床上主要用于阿片类药物中毒的急救、阿片类药物成瘾的诊断、麻醉镇痛药中毒的抢救，解救急性乙醇中毒，亦用作急性阿片类药物过量的诊断。近年来，很多临床试验及研究证明纳络酮对心肺脑复苏有重要价值[1,2]，美国急救医学会、中华医学会急救医学分会都将纳洛酮列人心肺脑复苏方案中。通常认为心跳骤停后β-内啡肽含量升高可抑制儿茶酚胺和前列腺素的心血管效应，使心肌收缩力下降，血压降低。用纳洛酮可以解除β-内啡肽抑制效应，儿茶酚胺释放增加[3,4]。除了阿片受体拮抗剂的作