生姜对NK_1受体介导的豚鼠离体回肠收缩影响

Effects of Ginger and its Pungent Constituents on Gastrointestinal Tract:Role of NK_1 Receptors in Isolated Ileum of Guinea Pig

目的 :观察生姜及其主要辛辣成分对NK_1受体介导的豚鼠离体肠管收缩的影响,从NK_1受体角度初步探讨生姜的止吐机制。方法:以豚鼠离体回肠为实验材料,利用恒温组织浴槽,在高中低三个浓度生姜汁(50μL、100μL、200μL)、6-姜酚(3×10-5mol·L^(-1)、1×10-5mol·L^(-1)、3×10-6mol·L^(-1))、6-姜烯酚(3×10-5mol·L^(-1)、1×10-5mol·L^(-1)、3×10-6mol·L^(-1))存在和不存在情况下,分别建立P物质(SP)和选择性NK_1受体激动剂GR73632的量效曲线,观察对肠管收缩和量效曲线的影响。结果:生姜汁、6-姜酚、6-姜烯酚均能剂量依赖性地抑制SP激发的离体肠管收缩增强,降低其平均张力(P<0.05,P<0.01或P<0.001);均可剂量依赖性地使SP的最大效应降低(P<0.001);除低浓度6-姜酚外,3个剂量的生姜汁、高中浓度的6-姜酚、3个浓度的6-姜烯酚对SP最大效应的抑制作用均显著强于SR140333(3×10-7mol·L^(-1)),与SR140333比较差异有统计学意义(P<0.001)。6-姜酚、6-姜烯酚均能剂量依赖性地抑制GR73632激发的离体肠管收缩增强,降低其平均张力(P<0.05或P<0.001);均可剂量依赖性地使GR73632的最大效应降低(P<0.001);高浓度6-姜酚和高浓度6-姜烯酚,对GR73632最大效应的抑制作用与阳性药SR140333(3×10-7mol·L^(-1))存在时比较均有增强趋势,但差异没有统计学意义(与SR140333比较,P>0.05)。生姜汁、6-姜酚、6-姜烯酚均可使SP的量效曲线非平行右移,并使最大效应显著降低;6-姜酚、6-姜烯酚均可使GR73632的量效曲线右移,并使最大效应显著降低。结论:生姜及其主要辛辣成分可以非竞争性阻断NK_1受体,这可能是生姜止吐作用的重要机制。

Objective ：To study contractility of guinea pig ileum in vitro ,and analyze the mechanism of anti- emetic effects of ginger and its pungent constituents. Methods：Using emesis-relating agonists as drugs,the inhibitory effects of ginger juice（50 μL, 100 μL,200 μL） ,6-gingero 6-shogaol（3 ×10^-5mol·L^-1,1 ×10^-5mol·L^-1,3 ×10^-6mol·L^-1） on 1 （3 ×10^-5mol·L^-1, 1 ×10^-5mol·L^-1, 3 ×10^-6mol·L^-1）, guinea pig ileum contractility in vitro were observed in organ bath. The contraction effect curve of substance P（SP） and GR73632（selective NKI receptor agonist） were established,respectively. Results：In the present of ginger juice,6-gingerol or 6-shogaol,SP exciting the contraction of isolated ileum was inhibited（P〈0.05,P〈0.01 or P〈0.001）. Ginger and its pungent constituents resulted in a dose-dependently reduction in the SP-indueed maximum responses （P〈0.001）. Compared with the SR140333（the positive control drug）,SP exciting the contraction of isolated ileum was inhibited in the present of ginger juice,6-gingerol or 6-shogaol except the 3×10^-6mol·L^-1 6-gingerol （P〈0.001）. In the present of 6-gingerol or 6-shogaol,GR73632 exciting the contraction of isolated ileum was inhibited（P〈0.05 or P〈0.001） and GR73632-indueed maximum responses were reduced（P〈0.001）. GR73632-indueed maximum responses were reduced in the present of 30 M 6-gingerol or 30 M 6-shogaol,but those resuhs had no satitistically significance（P〉0.05）. Ginger juice,6-gingerol or 6-shogaol the contractility dose-dependently,reduced the tone of ileum contractions stimulated by drugs could suppress and moved SP or GR73632 concentration-response curve nonparallel shift to the right. Conclusion：Ginger have an inhibitory effect on guinea pig ileum contractions, the mechanism might be non-competitively blocking NK1 receptor. The mechanisms of anti-emetic effect of ginger needs further study.