吗啉甲基萘满酮对胃肠道的作用及机制研究

Effect of 3,4-dihydro-2-(4-morpholinylmethyl)-1(2H)-naphthalenone on gastrointestinal tract and its mechanism

目的:探讨吗啉甲基萘满酮对胃肠道的作用及机制。方法:用腹泻指数法和炭末推进法观察低、中、高剂量(6.93,13.86和27.72 mg.kg-1)的吗啉甲基萘满酮对小鼠在体胃肠道的作用,通过离体标本运动实验法分析不同浓度(0.1,0.3,1 mmol.L-1)的吗啉甲基萘满酮对离体兔肠道平滑肌的作用。结果:在蓖麻油、硫酸镁和液体石蜡引起的小鼠腹泻模型中,吗啉甲基萘满酮中、高剂量组的小鼠腹泻指数同生理氯化钠溶液(NS)对照组相比均显著降低(P<0.05)。吗啉甲基萘满酮中、高剂量组的小鼠小肠炭末推进百分率也较NS组显著降低(P<0.05)。低、中、高浓度的吗啉甲基萘满酮均能显著降低肠平滑肌振幅(P<0.01),中浓度组还显著降低肠平滑肌张力(P<0.05),但各浓度组的小肠平滑肌自发活动的频率没有变化。结论:吗啉甲基萘满酮具有止泻的作用,其作用机制可能是降低肠管平滑肌振幅和张力。

Objective：To investigate the effect of 3,4-dihydro-2-（4-morpholinylmethyl）-1（2H）-naphthalenone（DHMMN） on gastrointestinal tract,and its mechanism.Methods： The diarrhea was induced by cathartics such as castor oil,MgSO4 and liquid paraffin in mice.Single DHMMN doses of 6.93,13.86 and 27.72mg·kg-1 were orally given.The diarrhea index was determined at various time points following dosing.The effect of DHMMN on the intestinal motion was evaluated by carbon powder transit method in vivo;that on smooth muscle contraction was observed in vitro in isolated small intestine from rabbits at concentrations of 0.1,0.3 and 1mmol·L-1.Results： Compared with saline control,DHMMN at 13.86 and 27.72mg·kg-1 significantly decreased the diarrhea index in the 3 kinds of diarrhea models（P〈0.05）,and reduced the percentage of carbon powder transit in intestine of mice（P〈0.05）.DHMMN significantly inhibited the contraction amplitude of isolated smooth muscles from rabbit small intestine at concentrations of 0.1,0.3 and 1mmol·L-1（P〈0.01）,decreased the tension of contraction at 0.3mmol·L-1（P〈0.05）,but did not affect the frequency of contraction at 0.1,0.3 and 1mmol·L-1.Conclusion： DHMMN possesses anti-diarrhea effect.Its possible mechanism relates to lowering the contraction amplitude and tension of small intestinal smooth muscles.