基于小鼠异食癖模型的常山碱盐呕吐机制

马丽娜; 李健; 李思迪; 代宝强; 张广平; 侯红平; 苏萍; 王凤玉; 叶祖光

doi:10.13422/j.cnki.syfjx.20191722

您当前的位置：

首页 >

文章列表页 >

基于小鼠异食癖模型的常山碱盐呕吐机制

药理 | 更新时间：2021-02-09

- 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
- 中国实验方剂学杂志 2019年25卷第22期页码：34-41
- 作者机构：
  
  中国中医科学院　中药研究所，博士后科研流动站，北京　 100700
- 作者简介：
  
  马丽娜，博士，助理研究员，从事中药药理与毒理学研究，E-mail：malina8512@163.com
  叶祖光，硕士，研究员，从事中药药理与毒理学研究，E-mail：zgye@icmm.ac.cn
- 基金信息：
  
  北京市自然科学基金项目(7174327)
- DOI：10.13422/j.cnki.syfjx.20191722
  中图分类号： R22; R242; R2-031; R285.5
- 收稿日期：2019-01-06，
  
  网络出版日期：2019-05-22，
  
  纸质出版日期：2019-11-20
- 稿件说明：
移动端阅览
马丽娜, 李健, 李思迪, 等. 基于小鼠异食癖模型的常山碱盐呕吐机制[J]. 中国实验方剂学杂志, 2019,25(22):34-41.

Li-na MA, Jian LI, Si-di LI, et al. Mechanism of Dichroa Alkali Salt Inducing Vomiting Based on Pica in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 34-41.
马丽娜, 李健, 李思迪, 等. 基于小鼠异食癖模型的常山碱盐呕吐机制[J]. 中国实验方剂学杂志, 2019,25(22):34-41. DOI： 10.13422/j.cnki.syfjx.20191722.

Li-na MA, Jian LI, Si-di LI, et al. Mechanism of Dichroa Alkali Salt Inducing Vomiting Based on Pica in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 34-41. DOI： 10.13422/j.cnki.syfjx.20191722.

摘要

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-HT

)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(

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(

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。

Abstract

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-HT

) 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

day after continuous administration and on the 1

day after drug administration (

0.01)

since the 3

day after administration

DAS-induced body mass loss of mice was significantly improved (

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.

关键词

Keywords

references

张昌绍，周廷冲．国产抗疟药材之研究(一)常山(临床实验报告) [J]．上海中医药杂志， 1955 ( 8 )： 29 ．

Pandey R K , Kumbhar B V , Srivastava S , et al . Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation [J]. J Biomol Struct Dyn , 2017 , 35 ( 1 ): 141 - 158 .

江文德，张昌绍，杨藻宸．常山碱催吐作用的研究—I．常山碱对鸽催吐作用的机制 [J]．上海第一医学院学报， 1957 ( 3 )： 253 - 258 ．

江文德．常山碱对狗催吐作用的机制 [J]．生理学报， 1961 ， 24 ( 3/4 )： 180 - 186 ．

Henderson F G , Rose C L , Harris P N , et al . γ-Dichroine, the antimalarial alkaloid of chang shan [J]. J Pharmacol Exp Ther , 1949 , 95 ( 2 ): 191 - 200 .

Rojas C , Slusher B S . Pharmacological mechanisms of 5-HT3 and tachykinin NK1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting [J]. Eur J Pharmacol , 2012 , 684 ( 1/3 ): 1 - 7 .

Saito R , Takano Y , Kamiya H . Roles of substance P and NK1 receptor in the brainstem in the development of emesis [J]. J Pharmacol Sci , 2003 , 91 ( 2 ): 87 - 94 .

GAN T J . Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? [J]. Cns Drugs , 2005 , 19 ( 3 ): 225 - 238 .

Fortin S M , Chartoff E H , Roitman M F . The aversive agent lithium chloride suppresses phasic dopamine release through central GLP-1 receptors [J]. Neuropsychopharmacol , 2016 , 41 ( 3 ): 906 - 915 .

CHOU T Q , FU F Y , KAO Y S . Antimalarial constituents of Chinese drug, chang shan, Dichroa febrifuga Lour [J]. J Am Chem Soc , 1948 , 70 ( 5 ): 1765 - 1767 .

Yamamoto K , Asano K , Matsukawa N , et al . Time-course analysis of pica in rats using an automatic feeding monitoring system [J]. J Pharmacol Toxicol , 2010 , 63 ( 1 ): 30 - 34 .

颜艳．灵芝多糖对顺铂诱导的小鼠异食癖和脑内Fos表达的影响 [D]．石家庄：河北师范大学， 2008 ．

李思迪，李春，代宝强，等．常山碱盐急性毒性及其与青蒿素类药物联合用药增效减毒作用 [J]．中国药理学与毒理学杂志， 2016 ， 30 ( 8 )： 808 - 814 ．

李健，杜江，马丽娜，等．常山碱盐灌胃给药抗疟药效及急性毒性 [J]．中国实验方剂学杂志， 2018 ， 24 ( 13 )： 141 - 146 ．

Rudd J A , Yamamoto K , Yamatodani A , et al . Differential action of ondansetron and dexamethasone to modify cisplatin-induced acute and delayed kaolin consumption (“pica”) in rats [J]. Eur J Pharmacol , 2002 , 454 ( 1 ): 47 - 52 .

Mehendale S R , Aung H H , YIN J J , et al . Effects of antioxidant herbs on chemotherapy-induced nausea and vomiting in a rat-pica model [J]. Am J Chinese Med , 2005 , 32 ( 6 ): 897 - 905 .

WANG C Z , Basila D , Aung H H , et al . Effects of Ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model [J]. Am J Chinese Med , 2005 , 33 ( 5 ): 807 - 815 .

Gershon M D . Review article: serotonin receptors and transporters－roles in normal and abnormal gastrointestinal motility [J]. Aliment Pharm Therap , 2004 , 20 : 3 - 14 .

Mawe G M , Hoffman J M . Serotonin signalling in the gut－functions, dysfunctions and therapeutic targets [J]. Nat Rev Gastroenterol Hepatol , 2013 , 10 ( 8 ): 473 - 486 .

王迎寒，刘玉玲，赵素微，等．腹泻型IBS脾虚肝郁证候与5-HT，CRH的相关性 [J]．中国实验方剂学杂志， 2017 ， 23 ( 18 )： 124 - 129 ．

陈锡强，刘可春，韩利文，等．醋酸直肠刺激对大鼠肠道P物质、5-HT免疫阳性神经纤维的影响 [J]．中国实验方剂学杂志， 2008 ， 14 ( 11 )： 71 - 73 ．

张婧娴，芮俊乾，陈逸凡，等．四逆散有效成分对内脏高敏感大鼠5-HT信号通路的多靶点协同调控 [J]．中国实验方剂学杂志， 2018 ， 24 ( 16 )： 115 - 123 ．

Mantyh P W . Neurobiology of substance P and the NK1 receptor [J]. J Clin Psychiat , 2002 , 63 : 6 - 10 .

Andrews P L R , Bhandari P . Resinferatoxin, an ultrapotent capsaicin analogue, has anti-emetic properties in the ferret [J]. Neuropharmacology , 1993 , 32 ( 8 ): 799 - 806 .

LAI J P , LAI S , Tuluc F , et al . Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor [J]. Proc Natl Acad Sci USA , 2008 , 105 ( 34 ): 12605 - 12610 .

Kennedy P G E , Rodgers J , Jennings F W , et al . A substance P antagonist, RP-67, 580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei [J]. Proc Natl Acad Sci USA , 1997 , 94 ( 8 ): 4167 - 4170 .

严晶，刘丽娜，陆茵，等．金荞麦提取物对肠易激综合征大鼠肥大细胞PAR-2，SP的影响 [J]．中国实验方剂学杂志， 2018 ， 24 ( 2 )： 92 - 97 ．

Bang R , Sass G , Kiemer A K , et al . Neurokinin-1 receptor antagonists CP-96, 345 and L-733, 060 protect mice from cytokine-mediated liver injury [J]. J Pharmacol Exp Ther , 2003 , 305 ( 1 ): 31 - 39 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

地黄块根中药效成分“配伍”特征及清热凉血功效

麻黄、细辛、附子配伍对过敏性鼻炎模型小鼠肺ILC2s相关因子的影响

上二黄丸通过调节胆汁酸代谢促进功能性便秘大鼠肠动力的配伍机制

基于超分子体系探究矿物药龙骨在含柴胡的角药配伍中的作用机制

基于代谢组学的四逆汤中附子-干姜药对配伍前后毒效变化规律分析