川芎嗪对正常人体肠系膜血管平滑肌细胞大电导钙激活钾通道的作用  

EFFECT OF TETRAMETHYLPYRAZINE ON LARGE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS OF HUMAN MESENTERIC ARTERY SMOOTH MUSCLE CELLS

作　　者：程俊[1] 曾晓荣[1] 李鹏云[1] 李妙龄[1] 谭晓秋[1] 周文[1] 杨艳[1] 

机构地区：[1]泸州医学院心肌电生理学研究室,四川泸州646000

出　　处：《泸州医学院学报》2011年第5期466-470,共5页Journal of Luzhou Medical College

基　　金：国家自然科学基金资助项目(30670763);四川省教育厅基金资助项目(10ZB123)

摘　　要：目的:研究川芎嗪((tetramethylpyrazine,TMP))对正常人体肠系膜血管平滑肌细胞大电导钙激活钾通道宏观电流(large-conductance Ca2+-activated potassium channels,BKCa)的作用,探讨TMP对BKCa的作用机制。方法:用急性酶分离法分离人体肠系膜动脉平滑肌细胞,采用全细胞穿孔膜片钳技术记录该细胞上的大电导钙激活钾通道宏观电流,并测试TMP对该电流的作用。结果:TMP在0.73、3.67mmol/L时可明显地可逆性地激活正常人体肠系膜血管平滑肌细胞上的BKCa,在0.73mmol/L浓度时,测试电压从-50～+60mV时差异都有统计学意义,其中测试电压在-50mV时,电流密度从0.25±0.03pA/pF增加到0.34±0.039pA/pF(P<0.01,n=12),测试电压在+60mV时,电流密度从8.37±1.75pA/pF增加到14.12±2.66pA/pF(P<0.01,n=12);TMP在3.67mmol/L时可明显地可逆性地激活正常人体肠系膜血管平滑肌细胞上的BKCa,测试电压从0～+60mV时差异都有统计学意义,其中测试电压在0mV时,电流密度从1.25±0.23pA/pF增加到1.90±0.31pA/pF(P<0.05,n=7),测试电压在+60mV时,电流密度从10.57±3.61pA/pF增加到20.32±4.68pA/pF(P<0.05,n=7)。但TMP在8.07mmol/L时可明显地可逆性地抑制正常人体肠系膜血管平滑肌细胞上的BKCa,测试电压从-60～+60mV时差异都有统计学意义,其中测试电压在-60mV时,电流密度从0.28±0.02pA/pF降低到0.15±0.04pA/pF(P<0.01,n=6),测试电压在+60mV时,电流密度从10.49±0.44pA/pF降低到1.83±0.68pA/pF(P<0.01,n=6)。结论:TMP在0.73、3.67mmol/L下,可激活正常人体肠系膜血管平滑肌细胞大电导钙激活钾通道,而在8.07mmol/L时可明显地可逆性地抑制正常人体肠系膜血管平滑肌细胞上的BKCa。在低浓度和较高浓度下TMP对正常人体肠系膜血管平滑肌细胞上的BKCa有不同效应的实验结果,为TMP应用于临床提供了实验依据。Objective： To research the effect of TMP on large-conductance calcium-activated potassium channels of human mesenteric artery smooth muscle cells,and discuss its mechanism.Methods： Acute enzyme method was applied to isolate human mesentery artery smooth muscle cells,the perforate whole cell patch technique was used to record the large-conductance Ca^2＋-activated potassium channel currents,and the effect of TMP on BKCa was detected.Results： At 0.73 and 3.67mmol/L,TMP could obviously activate BKCa on human mesenteric artery smooth muscle cells.At the dose of 0.73mmol/L,TMP could obviously increase current density of BKCa from-50 to ＋60mV.At-50 and ＋60mV,current density of BKCa respectively increase from 0.25±0.03pA/pF and 8.37±1.75pA/pF to 0.34±0.039 pA/pF（P〈0.01,n=12）and 14.12±2.66 pA/pF（P〈0.01,n=12）.At the dose of 0.73mmol/L,TMP could obviously increased current density of BKCa from 0 to ＋60mV.At 0 and ＋60mV,current density of BKCa respectively increased from 1.25±0.23pA/pF and 10.57±3.61pA/pF to 1.90±0.31pA/pF（P〈0.05,n=7）and 20.32±4.68pA/pF（P〈0.05,n=7） respectively.However,when the dose was 8.07mmol/L,TMP could obviously decrease current density of BKCa from-60 to ＋60mV.At-60 and ＋60mV,current density of BKCa decreased from 0.28±0.02pA/pF and 10.49±0.44pA/pF to 0.15±0.04pA/pF（P〈0.01,n=6）and 1.83±0.68pA/pF（P〈0.01,n=6）respectively.Conclusion： TMP can obviously activate BKCa on human mesenteric artery smooth muscle cells at 0.73 and 3.67mmol/L,but TMP can obviously inhibit BKCa on human mesenteric artery smooth muscle cells at 8.07mmol/L.Two different effects of TMP on BKCa human mesenteric artery smooth muscle cells at low and high concentration will provide the experimental basis for reasonable application of TMP in clinic.

关 键 词：川芎嗪 人体肠系膜血管 平滑肌细胞 大电导钙激活钾通道 

分 类 号：R33[医药卫生—人体生理学]