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SENSORY FUNCTION OF THE LIVER IN EMESIS

呕吐时肝脏的感觉功能

基本信息

批准号：
6139942
负责人：
MARK FRIEDMAN
金额：
$ 1.34万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-16 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6139942
关键词：
afferent nerve cyclophosphamide denervation dosage emesis ferrets liver metabolism liver pharmacology neurophysiology serotonin

项目摘要

Nausea and vomiting compromise the health and quality of life of patients with a variety of diseases, and create an obstacle to compliance with treatments that produce these disturbing side effects. Nausea and vomiting can be triggered by appropriate stimulation of several sites in the body, including the gastrointestinal tract and area postrema in the brainstem. The purpose of this project is to determine whether emetic agents and mediators also act in liver to generate a neural signal that triggers vomiting (emesis). Using the ferret, a standard animal model for studies the emetic reflex, we will: (1) Determine whether cyclophosphamide, which is used in cancer chemotherapy, acts in liver to induce emesis by comparing the effects of hepatic portal and jugular (systemic) infusion of different doses of this drug. (2) Determine whether the emetic mediator, 5-hydroxytryptamine (5HT) acts in liver to induce vomiting by comparing the effects of hepatic portal and jugular infusion of different concentrations of 5HT. (3) Investigate whether vagal sensory neurons transmit a hepatic signal for emesis by severing the nerves between the liver to brain. The results of this work should contribute to our knowledge of the mechanisms of nausea and vomiting, and may lead to the development of better treatments for these conditions.

恶心和呕吐损害了患有各种疾病的患者的健康和生活质量，并对产生这些令人不安的副作用的治疗的依从性造成障碍。恶心和呕吐可以通过适当刺激身体的几个部位来触发，包括胃肠道和脑干中的最后区。本项目的目的是确定催吐剂和介质是否也在肝脏中起作用，以产生触发呕吐（呕吐）的神经信号。本研究利用白鼬作为研究呕吐反射的标准动物模型，通过比较不同剂量环磷酰胺肝门静脉和颈静脉（全身）灌注的效应，确定肿瘤化疗中使用的环磷酰胺是否作用于肝脏引起呕吐。(2)通过比较肝门静脉和颈静脉输注不同浓度的5-羟色胺（5-HT）的催吐效应，确定催吐介质5-HT是否在肝脏中起催吐作用。(3)通过切断肝脏与大脑之间的神经，研究迷走神经感觉神经元是否传递呕吐的肝脏信号。这项工作的结果应该有助于我们了解恶心和呕吐的机制，并可能导致更好地治疗这些疾病的发展。