MN9202抑制心肌细胞收缩、舒张机制的研究  

Mechanism of inhibitory effect of MN9202 on contraction and relaxation functions of cardiac myocyte

作　　者：朱肖星[1] 梅其炳[1] 刘莉[1] 张峰[1] 裴建明[2] 张海锋[2] 胡玉珍[2] 陈定章[3] 牛小麟[4] 

机构地区：[1]第四军医大学药理学教研室,西安710032 [2]第四军医大学生理教研室,西安710032 [3]第四军医大学西京医院超声科 [4]西安交通大学第二医院心内科

出　　处：《解放军医学杂志》2005年第11期1022-1024,共3页Medical Journal of Chinese People's Liberation Army

摘　　要：目的研究MN9202对Forskolin(腺苷酸环化酶激动剂)、盐酸四乙胺(TEA,钙激活钾通道阻断剂)和美蓝(MB,鸟苷酸环化酶抑制剂)增强心肌细胞收缩、舒张功能影响的机制。方法采用IonOptix单细胞动缘检测系统(IonOptixCo.USA),测定心肌细胞收缩幅度和收缩/舒张速度等。这些指标均由计算机自动实时采集并记录。结果Forskolin、MB和TEA增强心肌细胞收缩幅度(ph)和心肌细胞收缩幅度/单个心肌细胞的长度百分比(ph/bl%),最大缩短速率(+dL/dt)和最大复长速率(-dL/dt),Forskolin和MB增强上述指标均有显著性差异(P<0.01)。Forskolin通过cAMP的增加发挥作用。MB通过减少cGMP的生成使心肌细胞的收缩功能增强。Forskolin增加ph、ph/bl%、+dL/dt和-dL/dt,上述指标分别增加91%、123%、110%、89%,用MB后,ph、ph/bl%、+dL/dt和-dL/dt分别为0.14±0.04μm、11±4%、2.2±0.3μm/s和2.2±0.6μm/s,用药前后差异非常显著(P<0.01)。3×10-6mol/L的MN9202降低Forskolin引起ph、ph/bl%、+dL/dt和-dL/dt的升高,其中+dL/dt和-dL/dt的降低较对照组显著差异。同时MN9202能降低MB和TEA引起ph、ph/bl%、+dL/dt和-dL/dt的增加。结论Forskolin、TEA和MB使心肌细胞收缩和舒张功能均增强,Forskolin能直接增加细胞内钙,TEA和MB能间接使细胞内钙增加而增强收缩功能;MN9202有抑制Forskolin、TEA和MB的作用。Objective To investigate the inhibitory effect on enhancement of contraction and relaxation functions of cardiomyocytes induced by of MN9202 TEA, Forskolin, and MB. Methods The twitch amplitude was measured with a video edge tracker method. The following indexes, including ph （peak height）, peak height/baseline percent （ph/bh %）, maximal velocity of contraction （＋dL/dt） and maximal velocity of diastolization （ -dL/dt）, were recorded by a computer. Results TEA, Forskolin and MB increased electricallyinduced contraction as shown by the following indexes： ph, ph/bl%, ＋dL/dt and -dL/dt. Forskolin and MB markedly augmented function of cardiac myocyte contraction and diastolization. Comparing with the control group, Forskolin （10-8mol/L） increased ph from 0. 12±0.03（urn）to 0. 24±0. 06 （um）, ph/bl% from 12±3% to 27±6%, ＋dL/dt from 1.8±0. 5 （um/s） to 3.8±0. 9 （um/s）, -dL/ dt from 1.8±0. 22 （um/s） to 3. 54±0. 7 （um/s）. These indexes increased by 91%, 123%, 110% and 89%, respectively. MB also increased significantly; ph, ph/bl%, ＋dL/dt and -dL/dt were 0. 14±0. 04um, 11±4%, 2. 2±0. 3um/s and 2. 2±0. 6um/s, respectively. MN9202 （3×10^-6 mol/L） decreased the indexes （＋dL/dt and -dL/dt ） which were increased by Forskolin significantly. Condusion TEA, Forskolin and MB increased function of cardiac myocyte contraction and diastolization. These drugs might elevate intracellular calcium content indirectly and directly. The effects of TEA, Forskolin and MB were attenuated by MN9202. MN9202 might not only block Dihydropyridine Receptor, but might also inhibit calcium influx. Further study is needed to elucidate exact mechanism of MN9202.

关 键 词：MN9202 心肌 收缩功能 舒张功能 

分 类 号：R331.31[医药卫生—人体生理学] R329.27[医药卫生—基础医学]