Ethanol/lipid metabolism, dysfunction of ion transport, and pathogenesis of alcoholic pancreatitis

乙醇/脂质代谢、离子转运功能障碍与酒精性胰腺炎的发病机制

基本信息

批准号：
15590638
负责人：
KONDO Takaharu
金额：
$ 1.86万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

1. Mutations and polymorphisms (TG repeats, poly T, M470V, Q1352H, R1453W) of CFTR (cystic fibrosis transmembrane conductance regulator) were examined in Japanese patients with chronic pancreatitis. None of the cystic fibrosis-causing mutations were detected. Frequency of the genotype TG(12/12) was higher in alcoholic pancreatitis. Frequency of the genotype V470/V470 was higher in idiopathic pancreatitis.2. To estimate CFTR Cl^- channel function, we established "finger sweat chloride test" to measure Cl^- concentration in insensible sweat, which sweat is collected by holding a small tube containing 100 μl water with the thumb and the sweat rate is measured by a perspiration meter. The Cl^- content in the sample is measured by capillary electrophoresis or more easily by a highly sensitive electrode.3. The activity of Na^+-H^+ exchange (NHE) in the apical membrane was examined in luminally-microperfused interlobular pancreatic duct segments isolated from ΔF mice, a cystic fibrosis model. The apical NHE activity significantly increased in ΔF/ΔF ducts, which may cause pH decrease of pancreatic juice.4. Effects of a series of short-chain alcohols (methanol, ethanol, propanol, and butanol) on cAMP-stimulated fluid secretion and intracellular Ca^<2+> concentration were examined in interlobular pancreatic duct segments isolated from guinea-pig. Methanol and ethanol enhanced fluid secretion and caused a transient increase of intracellular Ca^<2+>. On the contrary, propanol and butanol inhibited fluid secretion and lowered intracellular Ca^<2+>. This "cut-off effect" suggests alcohols act directly on some ion channels of pancreatic duct cells.

1。在日本的慢性胰腺炎患者中检查了CFTR的突变和多态性（TG重复，Poly T，M470V，Q1352H，R1453W）（囊性纤维化跨膜电导调节剂）。尚未检测到引起囊性纤维化突变。在酒精性胰腺炎中，基因型TG的频率（12/12）较高。特发性胰腺炎中基因型V470/V470的频率较高。2。为了估计CFTR CL^ - 通道功能，我们建立了“手指汗水氯化物测试”，以测量不敏感的汗液中的Cl^浓度，通过将含有100μl水的小管收集到带有拇指的100μl水和汗液速率的小管中，用汗液来收集汗液。样品中的Cl^ - 通过毛细管电泳或更容易通过高敏感的电极来测量。3。从囊性纤维化模型的ΔF小鼠中分离出的透明微膜间间间胰管段中，检查了根尖膜中Na^+-H^+交换（NHE）的活性。 ΔF/ΔF导管中的顶端NHE活性显着增加，这可能导致胰汁的pH降低。4。一系列短链醇（甲烷，乙醇，丙醇和丁醇）对cAMP刺激的液体分泌和细胞内Ca^<2+>浓度的影响在与豚鼠分离的腔间胰腺导管中进行了检查。甲烷和乙醇增强了液体分泌，并导致细胞内Ca^<2+>的短暂增加。相反，丙醇和丁醇抑制了液体分泌，并降低了细胞内Ca^<2+>。这种“截止效应”表明醇直接在胰管细胞的某些离子通道上作用。