瑞替加滨对离体大鼠十二指肠平滑肌收缩功能的影响及其机制

摘要

Objective To investigate the effect of retigabine on contraction of the smooth muscle of rat duodenum and to discuss its mechanism.Methods The rat duodenum was cut into segments with a length of about 1.5 cm.We used BL-420F Biological Function Experiment System for tension recording.After tension curve was stabilized, we performed the following experiments and each experiment was repeated 6 times.① We added 3.125, 6.25, 12.5, 25, 50, 100, 150, 200 μmol/L of retigabine into the solution.The recording time of each concentration was 15 min and each concentration was rinsed with Kreb's solution for 20 min.The mean amplitude of the smooth muscle tension of duodenum in vitro was measured before administration and after treatment with different concentrations of retigabine.② After 10 μmol/L XE-991 was added for 15 min, we added 20 μmol/L retigabine for 15 min.Then we compared the percent of mean amplitude of the smooth muscle tension of duodenum in vitro before and after retigabine.③ After 20 μmol/L retigabine was added for 15 min, we added 10 μmol/L XE-991 for 15 min.Then we compared the percent of mean amplitude of the smooth muscle tension of duodenum in vitro before and after XE-991.Results ① The percent of mean amplitude of the smooth muscle tension of duodenum in vitro before retigabine intervention was 100%.The percents of mean amplitude which were treated with retigabine were lower than that of the control group (0 μmol/L), P<0.05.In the range of 6.25-200 μmol/L, the percent of mean amplitude decreased gradually with the increase of retigabine concentration, P<0.05.② The percent of mean amplitude of smooth muscle tension which was incubated by XE-991 did not change significantly before and after retigabine intervention, P>0.05.③ The percent of mean amplitude of smooth muscle tension which was incubated by retigabine was higher than that after being given XE-991, P<0.05.Conclusion In the range of 6.25-200 μmol/L, retigabine can inhibit the contraction of rat duodenal smooth muscle in a dose-dependent manner, and this inhibitory effect may be due to the activation of potassium channel.%目的 探讨瑞替加滨对离体大鼠十二指肠平滑肌收缩功能的影响及其机制.方法 取大鼠十二指肠肠管剪成长度约1.5 cm的肠段,采用BL-420F生物机能实验系统持续记录张力曲线.十二指肠肠管张力曲线稳定后行以下试验:①依次予3.125、6.25、12.5、25、50、100、150、200 μmol/L的瑞替加滨溶液干预,每个浓度作用时间均为15 min,中间用Kreb′s溶液冲洗20 min.测量瑞替加滨干预前及各浓度干预后十二指肠肠管平滑肌张力曲线的平均振幅.②加入10 μmol/L XE-991作用15 min,再加入20 μmol/L瑞替加滨作用15 min.计算瑞替加滨加药前后离体十二指肠肠管平滑肌张力曲线的平均振幅变化百分率.③加入20 μmol/L瑞替加滨作用15 min,再加入10 μmol/L XE-991作用15 min.比较XE-991加药前后离体十二指肠肠管平滑肌张力曲线的平均振幅变化百分率.结果 ①瑞替加滨作用下离体十二指肠肠管平滑肌张力曲线的平均振幅(基线值)变化百分率为100%.各浓度瑞替加滨作用下张力曲线的平均振幅变化百分率均低于基线值,P均<0.05.在6.25~200 μmol/L范围内,随着瑞替加滨浓度增加提高,平均振幅变化百分率逐渐下降,P均<0.05.②瑞替加滨加药前后XE-991孵育的离体十二指肠肠管平滑肌张力曲线的平均振幅变化百分率无统计学差异,P>0.05.③XE-991加药后瑞替滨孵育的离体十二指肠肠管平滑肌张力曲线的平均振幅高于加药前,P<0.05.结论 瑞替加滨在6.25~200 μmol/L范围内可呈剂量依赖性抑制大鼠离体十二指肠平滑肌收缩;其机制可能为激活钾离子通道.