基于小鼠异食癖模型的常山碱盐呕吐机制

Mechanism of Dichroa Alkali Salt Inducing Vomiting Based on Pica in Mice

目的:探究常山碱盐(dichroa alkali salt,DAS)诱导呕吐的可能机制。方法:采用小鼠异食癖模型,分别观察3种不同机制的镇吐药,多巴胺受体拮抗剂甲氧氯普胺,5-羟色胺3(5-hydroxytryptamine 3,5-HT3)受体拮抗剂昂丹司琼,神经激肽-1受体拮抗剂阿瑞匹坦,对DAS所致小鼠体质量、正常饲料摄食量、高岭土摄食量及腹泻和死亡情况的影响,明确DAS可能的致吐途径;然后采用酶联免疫法针对性的检测DAS干预后不同时间点小鼠回肠和延髓中5-HT和P物质(substance P,SP)的表达情况,以确认DAS是否可影响这2种神经递质的变化。结果:配伍昂丹司琼和阿瑞匹坦后,连续给药第4天和药后第1天均可显著改善DAS诱导的小鼠摄食量降低现象(P <0. 01),自连续给药第3天起均可显著改善DAS诱导的小鼠体质量降低现象(P <0. 01),降低DAS诱导的小鼠腹泻率和死亡率,同时可有效拮抗DAS诱导的小鼠异食行为,但是甲氧氯普胺对上述指标则无明显改善作用;进一步检测呕吐相关神经递质,发现与空白组比较,给予DAS后4,12 h回肠和延髓中5-HT含量显著增加,48 h时回肠和延髓中SP含量显著升高。结论:小鼠异食模型可有效表征DAS诱导的呕吐现象,其诱导的呕吐行为可能与回肠和延髓中5-HT和SP含量升高有关,配伍昂丹司琼和阿瑞匹坦可有效拮抗DAS诱导的小鼠异食现象。

Objective:To study the possible mechanism of dichroa alkali salt(DAS)in inducing vomiting.Method:Mice pica model was used to observe the antagonistic effect of the three different kinds of antiemetic drugs[dopamine receptor antagonist metoclopramide,5-hydroxytryptamine 3(5-HT3)receptor antagonist ondansetron and neurokinin-1 receptor antagonist aprepitant]on body mass,food intake,kaolin consumption,diarrhea and death induced by DAS to preliminarily clarify the possible pathogenic pathway of DAS.Then,the expression of 5-HT and substance P(SP)in ileum and medulla of mice induced by DAS alone at different time points was detected by enzyme-linked immunosorbent assay to confirm whether DAS could affect the changes of these two neurotransmitters.Result:After treatment with ondansetron and aprepitant,DAS-induced reduction in food intake of mice was significantly improved on the 4 thday after continuous administration and on the 1 stday after drug administration(P<0.01),since the 3 rdday after administration,DAS-induced body mass loss of mice was significantly improved(P<0.01),and DAS-induced diarrhea and mortality in mice were significantly reduced,while DAS-induced pica in mice was effectively antagonized.However,metoclopramide did not significantly improve the above indicators.Further detection of vomiting-related neurotransmitters found that compared with the blank group,the expressions of 5-HT at 4 h,12 h and SP at 48 h after treatment with DAS were significantly increased in ileum and medulla of mice.Conclusion:The mice pica model can be used to effectively characterize DAS-induced vomiting.DAS-induced pica in mice may be associated with the increase of 5-HT and SP in ileum and medulla.Ondansetron and aprepitant can effectively antagonize DAS-induced pica in mice.