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氢溴酸槟榔碱对C57BL/6和W/W^v突变小鼠离体胃肠平滑肌条动力的作用研究
引用本文:王涛,陈其城,曹立幸,周吕,陈志强. 氢溴酸槟榔碱对C57BL/6和W/W^v突变小鼠离体胃肠平滑肌条动力的作用研究[J]. 中药新药与临床药理, 2020, 0(4): 425-434
作者姓名:王涛  陈其城  曹立幸  周吕  陈志强
作者单位:广州中医药大学第二临床医学院;广州中医药大学第二附属医院;中国医学科学院基础医学研究所
基金项目:广东省中医院外科国家(中医)区域诊疗中心建设项目(国中医药医政函[2018]205号);广东省中医院临床研究专项资助项目(YN10101902);广中医规划项目([2018]号-18);广东省财政厅项目(粤财工[2016]150-9);广东省中医药科学院科研专项(2018[75]YN2018ML11)。
摘    要:目的利用C57BL/6和W/W^v突变小鼠研究Cajal间质细胞(interstitial cells of Cajal,ICC)对小鼠胃肠各部位平滑肌条运动的影响,并通过胆碱能受体拮抗剂阿托品和钠通道阻断剂河豚毒素(tetrodotoxin,TTX)给药干预初步探讨氢溴酸槟榔碱(arecoline hydrobromide,Ah)促进小鼠平滑肌条动力作用的机制。方法制备C57BL/6和W/W^v突变小鼠胃肠各部位(胃体、胃窦、空肠和结肠)平滑肌环形肌条标本,分别观察和记录2种小鼠离体胃肠各部位平滑肌条的运动,比较2种小鼠胃肠各部位肌条收缩情况(收缩振幅、收缩频率和张力),并观察Ah对2种小鼠胃肠各部位肌条收缩的影响及阿托品、TTX对Ah促动力作用的干预。结果C57BL/6小鼠胃体部平滑肌环形肌条的收缩为具有较高振幅储存食物和低频率少量推进性的收缩波形,胃窦部为高振幅高张力较高频率推进性的收缩波形,空肠部为低振幅高频率快速推进性的收缩波形,结肠部为分散性中等振幅和频率的收缩波形;W/W^v突变小鼠胃体部环形肌条的收缩频率、收缩振幅都在较低水平,张力较其他部位偏高,胃窦部收缩频率、收缩振幅和张力都在较高水平,空肠部的收缩频率仍是最高,收缩振幅和张力却最低,结肠部的收缩频率最低,收缩振幅和张力处于中等水平;C57BL/6小鼠各部位肌条的收缩力均远大于W/W^v突变小鼠(P<0.05,P<0.01,P<0.001);Ah能明显增加C57BL/6小鼠各部位肌条的收缩力(P<0.05,P<0.01,P<0.001),对W/W^v突变小鼠各部位肌条的收缩力只有轻微增加(P<0.05,P<0.001);阿托品能抑制Ah的促动力作用,而TTX并不能阻断。结论ICCs在调控小鼠胃肠平滑肌条运动中具有重要作用,氢溴酸槟榔碱的促动力作用机制除了ICCs网络的调控外,还有一部分神经调控。另外,氢溴酸槟榔碱可能是经M型受体起作用的。

关 键 词:氢溴酸槟榔碱  C57BL/6小鼠  W/Wv突变小鼠  离体胃肠平滑肌条动力  阿托品  河豚毒素

Effect of Arecoline Hydrobromide on Motility of Gastrointestinal Smooth Muscle Strips Isolated from C57BL/6 and W/W^v Mutant Mice
WANG Tao,CHEN Qicheng,CAO Lixing,ZHOU Lyu,CHEN Zhiqiang. Effect of Arecoline Hydrobromide on Motility of Gastrointestinal Smooth Muscle Strips Isolated from C57BL/6 and W/W^v Mutant Mice[J]. Traditional Chinese Drug Research & Clinical Pharmacology, 2020, 0(4): 425-434
Authors:WANG Tao  CHEN Qicheng  CAO Lixing  ZHOU Lyu  CHEN Zhiqiang
Affiliation:(The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;The Second Affiliated.Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China;Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing 100730,China)
Abstract:Objective C57 BL/6 and W/W^v mutant mice were used to study the effects of interstitial cells of Cajal(ICC)on motility of smooth muscle strip isolated from various parts of gastrointestinal tract of mice. The mechanism of arecoline hydrobromide(Ah) promoting smooth muscle strip motility in mice was preliminarily explored using cholinergic receptor antagonist atropine and sodium channel blocker tetrodotoxin(TTX). Methods The circular smooth muscle strips of the gastrointestinal tract(gastric body,gastric antrum,jejunum and colon)of C57 BL/6 and W/W^v mutant mice were prepared. The movement of the smooth muscle strips of the gastrointestinal tract of the two kinds of mice was observed and recorded respectively. The contractions(contraction amplitude,contraction frequency and tension)of the muscle strips of the gastrointestinal tract of the two kinds of mice were compared. The effects of Ah on the contractions of muscle strips in the gastrointestinal tract of two kinds of mice and the intervention of atropine and TTX on the promotion of Ah were observed. Results In C57 BL/6 mice,the contractions of smooth muscle circular strips of gastric body are of high amplitude for storing food and low frequency for a small amount of propulsive contractions. In gastric antrum,the contractions are of high amplitude,high tension and high frequency for propulsive contractions. In jejunum,the contractions are of low amplitude,high frequency and rapid propulsive contractions. In colon,the contractions are of dispersive,medium amplitude and frequency. In W/W^v mutant mice,the contraction frequency and amplitude of gastric body circular muscle strips were lower,the tension was higher than other parts;the contraction frequency,amplitude and tension of gastric antrum were higher;the contraction frequency of jejunum was still the highest, the contraction amplitude and tension were the lowest;and the contraction frequency of colon was the lowest,the contraction amplitude and tension were in the middle level. In C57 BL/6 mice,the contractile force of muscle strips was much greater than that of W/W^v mutant mice(P < 0.05,P < 0.01,P < 0.001). Ah can significantly increase the contractile force of muscle strips in C57 BL/6 mice(P <0.05,P < 0.01,P < 0.001);and only slightly increase the contractive force in W/W^v mutant mice(P < 0.05,P <0.001). Atropine can inhibit the promotion of Ah,but TTX cannot block it. Conclusion ICCs play an important role in regulating the movement of gastrointestinal smooth muscle strips in mice. Besides the regulation of ICCs network,there are also some neural regulation in the mechanism of Ah. In addition,Ah may act through M-type receptor.
Keywords:Arecoline hydrobromide  C57BL/6 mice  W/Wv mutant mice  motility of isolated gastrointestinal smooth muscle strips  atropine  tetrodotoxin
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