甘草次酸对大鼠心室肌细胞L型钙离子电流的影响  

Effect of Glycyrrhetic Acid on the L-type Calcium Current of Ventricular Myocardial Cells of the Rat

作　　者：谢世荣 宋志国[2] 于新宇[3] 孙长滨[3] 黄彩云[1] 黄胜英[1] 刘琳[4] 

机构地区：[1]大连大学医学院药理学教研室,116622 [2]中国医科大学药理学教研室,沈阳110001 [3]大连大学医学院组织胚胎学教研室,116622 [4]大连大学医学院预防医学教研室,116622

出　　处：《医药导报》2005年第8期665-667,共3页Herald of Medicine

基　　金：大连市科委科研项目(基金编号:2002B4-NS048)

摘　　要：目的观察甘草次酸(glycyrrheticacid,Gta)对大鼠单一心室肌细胞L型钙离子电流(ICa-L)的影响。方法以Langendoff匀速灌流体外大鼠心脏,Ⅰ型胶原酶酶解分离单一大鼠心室肌细胞,将心室肌细胞悬液放入容积为0.2~0.3mL的浴槽内,间隔相同时间分别向浴槽内加入0.1,1.0,10.0μmol·L-1Gta,应用全细胞膜片钳技术记录不同浓度Gta对单一大鼠心室肌细胞ICa-L的影响;保持电位为-30mV、指令电位为-40^+60mV、步阶脉冲为10mV、时程为300ms、刺激频率为0.5Hz的条件下,引出钙离子电流,取指令电位与相对应的钙离子通道电流作用结果制作不同浓度Gta下L型钙离子通道的电流-电压(I-V)关系曲线。结果Gta浓度分别为0.1,1.0,10.0μmo1·L-1时可剂量依赖性地降低ICa-L,分别使ICa-L从加入Gta前的(2.30±0.29)nA降至(1.96±0.34),(1.37±0.24),(0.66±0.20)nA(与加入Gta前比较,均P<0.01);Gta0.1,1.0,10.0μmo1·L-1也可抑制L型钙离子I-V曲线,使I-V曲线上移,但峰值电流不变。结论Gta通过阻滞L型钙通道抑制L型钙离子内流,这种机制可能与Gta抗心律失常作用有关。Objective To survey the effect of glycyrrhetic acid (Gta) on the L-type calcium current of single ventricular myocardial cells of the rat. Methods Adult Wistar rats of both sexes served as the subjects of the experiment. The isolated rat heart was submitted to constant-speed perfusion with a Langendorff device. Single ventricular myocytes were isolated from the rats heart by emzymolysis with the use of type Ⅰcollagenase. A small amount of the suspension of myocytes was instilled into a bath with a volume of 0.2-0.3 mL. 0.1, 1.0 and 10.0 mo1·L^-1 of Gta were then successively added into the bath with equal time intervals. Whole-cell patch-clamp technique was used to record the effect of Gta in different concentrations on the L-type Ca^2+ current (I_ca-L) of single rat ventricular myocytes. The Ca^2+ current was elicited under those conditions in which the retention potential was 30 mv, the instruction potential was -40-±60 mv, the steps pulse was 10 mv, the duration was 300 ms, and the stimulus frequency,0.5 Hz .The current-voltage (I-V) curve of I_ca-L in different concentrations of Gta was plotted with the instruction potential and the results of the action of the corresponding Ca^2+ channel current. Results Gta in concentration of 0.1,1.0 and 10.0 μmol·L^-l was shown to reduce I_ca-L in a dose-dependent manner: the I_ca-L value before the addition of Gta (2.30±0.29)nA was lowered to (1.96±0.34), (1.37±0.24) and (0.66±0.20) nA, respectively (P<0.01). Gta in concentrations of 0.1,1.0 and 10.0 μmol·L^-l could also inhibit the I-V curve of I_ca-L, causing it to move upward, while the I_Ca-max remained unchanged. Conclusion Gta was shown to inhibit the inflow of L-type Ca^2+ by blocking the L-type Ca^2+ channel. This action of Gta may be related to its antiarrhythmic effect.

关 键 词：甘草次酸 心室肌细胞 L型钙离子电流 膜片钳技术 

分 类 号：R972.2[医药卫生—药品] R966[医药卫生—药学]