Effects of Ethanol on Pancreas Regeneration

乙醇对胰腺再生的影响

• 批准号: 7256193
• 负责人: Dahn Louis Clemens
• 金额: $ 18.11万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256193
• 关键词: Acinar Cell; Activities of Daily Living; Acute; Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol dehydrogenase; Alcoholic Pancreatitis; Animals; Applications Grants; Biochemical Pathway; Clinical; Coxsackie Viruses; Coxsackievirus Infections; Cytochrome P-450 CYP2E1; Data; Development; Disease; Ethanol; Etiology; Exploratory/Developmental Grant; Foundations; Future; Growth Factor; Histologic; Human; Impairment; Infection; Inflammation; Liver; Liver Regeneration; Mediating; Modeling; Molecular; Mus; Natural regeneration; Organ; Pancreas; Pancreatitis; Personal Satisfaction; Research; Signal Transduction; Suggestion; Testing; Thinking; Tissues; Virus Diseases; acute pancreatitis; alcohol effect; base; cell injury; chronic alcohol ingestion; day; design; feeding

DESCRIPTION (provided by applicant): Alcohol abuse is often associated with acute pancreatitis, but the mechanisms by which ethanol sensitizes or predisposes the pancreas to damage are not clear. Acute pancreatitis is characterized by inflammation and damage to the pancreatic acinar cells. It is generally thought, on the basis of clinical observations and animal studies, that, after an acute episode of pancreatitis, the pancreas regenerates to its full structural and functional capacity within 12-14 days. The pancreas and the liver are developmentally related and both organs express alcohol dehydrogenase and cytochrome P450 2E1. Additionally, alcohol abuse is associated with disease in both organs. It is well established that ethanol consumption impairs liver regeneration. Thus, we speculated that ethanol consumption would also impair pancreatic regeneration. In preliminary studies, using a murine model of alcoholic pancreatitis that combines ethanol feeding and pancreatic damage induced by coxsackievirus infection, we have investigated this possibility. On the basis of histologic and enzymatic data our preliminary results support the suggestion that ethanol feeding impairs pancreas regeneration. It has been shown that regeneration of the pancreas requires the tightly orchestrated, coordinated actions of specific growth factors. It is well documented that ethanol consumption can alter the expression and signaling of growth factors. Therefore, it is our hypothesis that ethanol consumption impairs the ability of the pancreas to regenerate to its full structural and functional capacity after severe damage, and this impairment is mediated by aberrant temporal or quantitative expression of specific growth factors. To test this hypothesis, we propose the following specific aims: 1) To further characterize the ethanol-induced impairment in pancreas regeneration after virally induced pancreatitis 2) To determine the molecular mechanisms responsible for the ethanolinduced impairment in pancreas regeneration. Completion of these specific aims will provide new and important information about the effects of ethanol on pancreatic regeneration, as well as forming the foundation for future studies to determine the molecular and biochemical pathways that are affected by chronic ethanol consumption and result in this ethanol-mediated impairment of regeneration.

描述（由申请人提供）：酒精滥用通常与急性胰腺炎相关，但乙醇致敏或使胰腺易于损伤的机制尚不清楚。急性胰腺炎的特征是胰腺腺泡细胞的炎症和损伤。基于临床观察和动物研究，通常认为，在急性胰腺炎发作后，胰腺在12-14天内再生到其全部结构和功能能力。胰腺和肝脏是发育相关的，两个器官都表达乙醇脱氢酶和细胞色素P450 2 E1。此外，酒精滥用与两个器官的疾病有关。众所周知，乙醇消耗会损害肝脏再生。因此，我们推测乙醇消耗也会损害胰腺再生。在初步研究中，我们使用酒精性胰腺炎小鼠模型，结合酒精喂养和柯萨奇病毒感染引起的胰腺损伤，研究了这种可能性。基于组织学和酶的数据，我们的初步结果支持乙醇喂养损害胰腺再生的建议。已经表明，胰腺的再生需要特定生长因子的紧密协调和协调作用。有充分的证据表明，乙醇消耗可以改变生长因子的表达和信号传导。因此，我们的假设是，酒精消耗损害胰腺的能力，以再生到其完整的结构和功能的能力，严重损伤后，这种损害是由异常的时间或特定的生长因子的定量表达介导的。为了验证这一假设，我们提出了以下具体目标：1）进一步表征病毒诱导的胰腺炎后乙醇诱导的胰腺再生障碍2）确定负责乙醇诱导的胰腺再生障碍的分子机制。这些具体目标的完成将提供有关乙醇对胰腺再生影响的新的重要信息，并为未来的研究奠定基础，以确定受慢性乙醇消耗影响并导致乙醇介导的再生障碍的分子和生化途径。