ROLE FOR VIRAL INFECTION IN ALCOHOLIC PANCREATITIS

病毒感染在酒精性胰腺炎中的作用

• 批准号: 6681050
• 负责人: THOMAS R JERRELLS
• 金额: $ 14.23万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681050
• 关键词: Coxsackievirus; alcoholic beverage consumption; alcoholism /alcohol abuse; cytokine; dietary lipid; disease /disorder etiology; disease /disorder model; disease /disorder proneness /risk; ethanol; fibrosis; genetic strain; genetic susceptibility; histopathology; host organism interaction; laboratory mouse; model design /development; nutrition related tag; pancreas; pancreatitis; pathologic process; toxicology; virus diseases; virus infection mechanism

DESCRIPTION (provided by applicant): A large proportion of the cases of pancreatitis in human beings are associated with alcohol consumption, but pancreatitis develops in only a minority of people who abuse alcohol. These observations support the argument that factors other than alcohol or alcohol metabolisms are involved in the development of alcoholic pancreatitis. The hypothesis that will be investigated by the research proposed in this exploratory/developmental grant application is that one co-factor for the development of acute and chronic alcoholic pancreatitis is an infection with a virus that has a tropism for the pancreas. This viral infection is hypothesized to initiate the damage in the pancreas and this damage is more severe in individuals who abuse alcohol through an alcohol-associated sensitization of the pancreas. A murine model of alcohol consumption that is done with the use of C57BL/6 and Balb/c mice provided ethanol (ETOH) in either a liquid diet or in the drinking water will be used for these studies. Specifically, mice provided ETOH and control mice (i.e., pair-fed and chow-fed) will be infected with coxsackievirus group B, stereotype 3 (CVB3) and pancreas damage and fibrosis will be evaluated. The hypotheses will be addressed by three specific aims: 1) To develop the model system to characterize the effects of ETOH and CVB3 infection of the pancreas; 2) To determine the effect of ETOH consumption on production of pro-inflammatory cytokines during the viral infection; 3) To determine the effects of chronic ETOH consumption, with an ETOH-in-drinking-water model system, on pathologic effects in the pancreas after viral infection. The development and characterization of this model system will provide a useful model of alcoholic pancreatitis that will allow follow-up studies to investigate mechanisms of ETOH to sensitize the pancreas to damage. The model system will also allow critical studies of possible therapeutic interventions.

描述（由申请人提供）： 人类大部分胰腺炎病例与饮酒有关，但只有少数酗酒者会患上胰腺炎。这些观察结果支持这样的论点：酒精或酒精代谢以外的因素也参与了酒精性胰腺炎的发生。这项探索性/发展资助申请中提出的研究将调查的假设是，急性和慢性酒精性胰腺炎发展的一个辅助因素是对胰腺有趋向性的病毒感染。据推测，这种病毒感染会引发胰腺损伤，并且由于酒精相关的胰腺过敏，这种损伤对于酗酒的人来说更为严重。这些研究将使用 C57BL/6 和 Balb/c 小鼠建立的小鼠饮酒模型，并在流质饮食或饮用水中提供乙醇 (ETOH)。具体来说，提供 ETOH 的小鼠和对照小鼠（即配对喂养和食物喂养）将感染柯萨奇病毒 B 组、刻板型 3 (CVB3)，并评估胰腺损伤和纤维化。 这些假设将通过三个具体目标来实现：1）开发模型系统来表征 ETOH 和 CVB3 感染对胰腺的影响； 2) 确定病毒感染期间消耗乙醇对促炎细胞因子产生的影响； 3) 使用饮用水中的 ETOH 模型系统确定慢性 ETOH 消耗对病毒感染后胰腺病理影响的影响。该模型系统的开发和表征将提供一个有用的酒精性胰腺炎模型，使后续研究能够调查 ETOH 使胰腺对损伤敏感的机制。该模型系统还将允许对可能的治疗干预措施进行批判性研究。