马来酸曲美布汀对寒冷束缚应激大鼠结肠平滑肌细胞离子通道的作用  

Effect of trimebutine maleate on ion channels in colon smooth muscle cell of cold restraint stress inducedrats

作　　者：郭凌云[1] 李俊霞[1] 苗林[2] 迟雁[1] 王化虹[1] 姬广聚[2] 刘新光[1] 

机构地区：[1]北京大学第一医院消化内科,100034 [2]中国科学院生物物理研究所

出　　处：《中华消化杂志》2012年第7期450-454,共5页Chinese Journal of Digestion

基　　金：国家自然科学基金（30840045）

摘　　要：目的探讨马来酸曲美布汀（TM）对寒冷束缚应激（CRS）大鼠结肠平滑肌细胞大电导钙激活的钾通道（BKCa）及雷诺定受体（RyR）mRNA和蛋白表达的影响。方法24只Wistar大鼠均分为CRS组、CRS＋TM组和对照组，CRS组大鼠每日按6ml／kg予0．9％NaCl溶液灌胃，CRS＋TM组大鼠每日按6ml／kg予15g／LTM灌胃，置铁丝笼中，在4℃环境限制活动2h，连续5d。对照组大鼠按6ml／kg予0．9％NaCl溶液灌胃1次，不予应激。观察各组大鼠排便量和粪便性状改变，分离结肠平滑肌组织进行RT-PCR和Western印迹分析测定BKCa以及RyRz通道mRNA和蛋白的表达。结果CRS组大鼠排便颗粒中位数为6，对照组为1，CRS＋TM组为5，肉眼观察CRS组及CRS＋TM组大鼠粪便外观较对照组稀，含水量多。与对照组比较，CRS组及CRS＋TM组大鼠结肠组织无明显病理学改变。对照组与CRS组大鼠结肠平滑肌细胞BKCa和RyR2mRNA表达无明显差异，CRS＋TM组BKCa mRNA表达较对照组上调1.45倍，CRS＋TM组RyRzmRNA较对照组上调1．32倍。与对照组相比，CRS组大鼠结肠平滑肌细胞BKCa和RyRz蛋白表达无明显差异，CRS＋TM组BKCa蛋白较对照组表达上调1．39倍，未见RyRz蛋白表达条带。结论TM对CRS大鼠结肠平滑肌收缩的影响可能是通过大鼠结肠平滑肌细胞BKCa通道mRNA、蛋白表达上调和RyRmRNA表达上调而起作用。Objective To investigate the effects of trimebutine maleate （TM） on the expression of large conductance calcium-activated potassium channel （BKCa） and ryanodine receptors （RyR） channels at mRNA and protein level in colonic smooth muscle cell of cold restraint stress （CRS） induced rats. Methods A total of 24 Wistar rats were divided into CRS group, CRS with TM group and control group equally. The rats of CRS group were gavaged with 0.9%NaC1 （6 ml/kg） daily; the rats of CRS with TM group were gavaged with 15 g/L TM （6 ml/kg） daily and activity was restricted in wire cage at 4 ℃ for two hours, continuously for five days. The rats of control group were gavaged with 0.9%NaC1 （6 ml/kg） once without CRS. The amount and characteristics of stool of rats in each group were observed. The colonic smooth muscle was isolated to detect the expression of BKCa andRyR at mRNA and protein level by reverse transcription-polymerase chain reaction （RT-PCR） and Western Blot. Results The median of rats defecation particles of CRS group was six, control group was one and CRS with TM group was five. Compared with control group, the defecation appearance of CRS group and CRS with TM group was looser and wetter observed by naked eyes. Compared with control group, there was no obvious pathological changes in CRS and CRS with TM group. There was no significant difference in the mRNA expression of BKc, and RyR channels between control group and CRS group. Compared with control group, the BKc. expression at mRNA level of CRS with TM group increased 1.45 fold. Compared with control group, the RyRz expression at mRNA level of CRS with TM group increased 1.32 fold. Compared with control group, the BKco expression at protein level of CRS with TM group increased 1. 39 fold, and there was no RyR2 expression band at protein level. Conclusion TM might affect colonic smooth muscle contraction through the upregulation of BKco expression at mRNA and protein level and RyR expression at mRNA level.

关 键 词：马来酸盐类 曲美布汀 应激 肌 平滑 结肠 钾通道 钙激活 兰尼碱受体钙释 放通道 

分 类 号：R9[医药卫生—药学]