海南医科大学学报2025,Vol.31Issue(17):1308-1317,10.DOI:10.13210/j.cnki.jhmu.20240921.001
基于PPTA/SP/NK1信号通路探讨橘百芍合方治疗化疗性异食癖恶心呕吐模型大鼠的作用机制
Mechanism of action of JuBaiShao Combination Formula on model of cisplatin-induced nausea and vomiting in rats based on the PPTA/SP/NK1 signaling pathway
摘要
Abstract
Objective:To study the mechanism of Jubaishao combination formula on chemotherapeutic pica nausea and vomit-ing model rats based on PPTA/SP/NK1 signaling pathway.Methods:A total of 48 SPF Wistar male rats were randomly as-signed to six groups,including normal control group,cisplatin model group,aprepitant group(2 mg/kg),Jupaeone low-dose group(1.8 g/kg),Jupaeone medium-dose group(3.6 g/kg)and Jupaeone high-dose group(7.2 g/kg),with eight rats in each group.Except for the normal control group,the rats with pica nausea and vomiting model were treated with 5 mg/kg cisplatin in-traperitoneally in other groups.The animals in each group were given intragastric treatment for the first time one hour before mod-eling and 12 hours after modeling.The consumption of kaolin within 72 hours before and after modeling was observed and record-ed.Serum,ileum and medulla oblongata tissues were collected from the animals 24 h and 72 h after anesthesia.The content of Substance P(SP)in serum and medulla oblongata was determined by ELISA.The expression of Neurokinin-1(neurokinin-1,NK1)receptor in the ileum and medulla oblongata of rats was detected by immunohistochemical staining.The mRNA expression levels of Preprotachykinin-A(PPTA)and NK1 receptor in ileum and medulla oblongata were detected by Real-time PCR.West-ern Blotting method was used to determine the NK1 receptor protein in rat ileum and medulla oblongata.Results:At 24 h and 72 h after cisplatin modeling,the intake of kaolin in model group was notably enhanced compared with the normal control group(P<0.05).The intake of kaolin in aprepitant group and Jubaishao high-dose group was significantly decreased at 24 h and 72 h after modeling compared with that in model group(P<0.05).Compared with normal control group,SP content in serum and medulla oblongata of model group was notably enhanced at 24 h and 72 h after modeling(P<0.05).The content of SP in serum and medul-la oblongata of aprepitant group,Jubaishao medium dose group and Jubaishao high dose group was significantly decreased at 24 h and 72 h after model building compared with that of model group(P<0.05).Compared with normal control group,PPTA mRNA,NK1 receptor protein and NK1 receptor mRNA in rat ileum and medulla oblongata of model group were significantly in-creased at 24 h and 72 h after modelling(P<0.05).Compared with model group,PPTA mRNA,NK1 receptor protein and NK1 receptor mRNA in ileum and medulla oblongata of aprepitant group,Jubaishao group and medium and high dose group were signif-icantly decreased at 24 h and 72 h after model building(P<0.05).Conclusion:Jubaishao may exert its antiemetic effect by inhibit-ing central and peripheral PPTA/SP/NK1 pathways.关键词
橘百芍合方/化疗性呕吐/PPTA/SP/NK1信号通路/异食癖/大鼠Key words
JuBaiSao Combination Formula/Chemotherapeutic nausea and vomiting/PPTA/SP/NK1 signaling pathway/Pica/Rat分类
医药卫生引用本文复制引用
周黎阳,陈萍,丁春丽..基于PPTA/SP/NK1信号通路探讨橘百芍合方治疗化疗性异食癖恶心呕吐模型大鼠的作用机制[J].海南医科大学学报,2025,31(17):1308-1317,10.基金项目
This study was supported by National Administration of Traditional Chinese Medicine Science and Technology Project(GZY-KJS-2022-041-1) 国家中医药管理局科技项目(GZY-KJS-2022-041-1) (GZY-KJS-2022-041-1)