SENSORY FUNCTION OF THE LIVER IN EMESIS

恶心和呕吐损害了各种疾病患者的健康和生活质量，并造成了产生这些令人不安的副作用的治疗依从性的障碍。适当刺激身体的几个部位，包括胃肠道和脑干的后脑区，可引起恶心和呕吐。该项目的目的是确定催吐剂和介质是否也在肝脏中起作用，产生触发呕吐（呕吐）的神经信号。我们将利用研究吐吐反射的标准动物模型雪貂：(1)通过比较不同剂量环磷酰胺在肝门静脉和颈静脉（全身）输注的效果，确定用于癌症化疗的环磷酰胺是否在肝脏中引起吐吐。(2)通过比较肝门静脉和颈静脉输注不同浓度5HT的效果，确定催吐介质5-羟色胺（5-hydroxytryptamine, 5HT）是否在肝脏中起诱导呕吐作用。(3)探讨迷走神经感觉神经元是否通过切断肝脑间神经传递肝脏呕吐信号。这项工作的结果应该有助于我们了解恶心和呕吐的机制，并可能导致更好的治疗这些疾病的发展。

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.