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MEMBRANE-BINDING COMPLEMENT REGULATORY FACTER IN GASTROINTESTINAL TRACT

胃肠道中的膜结合补体调节因子

基本信息

批准号：
08670607
负责人：
JOH Takashi
金额：
$ 1.28万
依托单位：
NAGOYA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670607/
关键词：
COMPLEMENT COMPLEMENT REGULATORY PROTEIN MUCOSAL INJURY MUCOSAL IMMUNITY DAF 粘膜障害

项目摘要

In this study, complement and its regulatory system were investigated in the rat, human, and guinea pig gastrointestinal tract. Roles of complement and plasma carboxypeptidase (CP ; inactivator of C3a and C5a) in systemic shock following intestinal ischemia were studied using cobra venom factor (CVF,which reduced serum complement to undetectable level) and/or CP inhibitor. Pretreatment with CVF prevented, but CP inhibitor aggravated such a shock. In human gastric mucosa, DAF (membrane binding inhibitor of complement) was found to be unregulated during gastritis. The study on guinea pig gastric mucosa clearly demonstrated alternation in the expression of DAF gene and protein after gastric I/R.Expression of DAF mRNA was constitutively demonstrated in normal guinea pig gastric mucosa and was most intense in 6hr after I/R.However, it was detected at normal levels at 24 hr, 3 and 7 days. Expression of DAF protein was not significant from 0 to 12 hr after I/R but it was increased in amount at 24 hr and 3 days, returning to less than significant levels at 7 days. Expression of DAF isoform mRNA was also assessed by RT-PCR with specific primers for 6 isoforms (transmembrane types ; TM-a, TM-ab, TM-abc, and glycosylphosphatidyl-inositol anchored types ; GPI-a, GPI-ab, GPI-abc) were evaluated. Messenger RNAs for GPI-a, GPI-ab, GPI-abc, TM-a and TM-ab were constitutively detected in normal guinea pig gastric mucosa, whereas mRNA for TM-abc was not. However, 6 hr after I/R,mRNAs for TM-abc became detectable, with TM-a and TM-ab the dominant species. We also evaluated role of complement in a rat model for ischemia-induced gastric mucosal injury. Pretreatments with CVF and K-76 COOH,a inhibiter of complement action, significantly attenuated mucosal injury observed after reperfusion.These findings support that complement and its regulatory system may play a significant role in pathology of gastrointestinal tract.

在这项研究中，补体及其调节系统进行了研究，在大鼠，人类和豚鼠胃肠道。本文应用眼镜蛇毒因子（CVF）和/或血浆羧肽酶（CP）抑制剂，研究了补体和CP在肠缺血性休克中的作用。CVF预处理可防止休克的发生，而CP抑制剂可加重休克的发生。在人胃粘膜中，发现补体膜结合抑制剂（membrane binding inhibitor of complement，EIB）在胃炎期间不受调节。对豚鼠胃粘膜的研究清楚地表明，胃I/R后，GSTmRNA和蛋白质的表达发生了变化。GSTmRNA在正常豚鼠胃粘膜中呈组成性表达，在I/R后6小时表达最强，但在24小时、3天和7天仍能检测到正常水平。在I/R后0 - 12小时，α-淀粉样蛋白的表达不显著，但在24小时和3天时其量增加，在7天时恢复到低于显著水平。还通过RT-PCR用6种同种型（跨膜型; TM-a、TM-ab、TM-abc和糖基磷脂酰肌醇锚定型; GPI-a、GPI-ab、GPI-abc）的特异性引物评估GPI-a亚型mRNA的表达。在正常豚鼠胃粘膜中组成型检测到GPI-a、GPI-ab、GPI-abc、TM-a和TM-ab的信使RNA，而TM-abc的mRNA则未检测到。然而，在I/R后6小时，TM-abc的mRNA变得可检测，其中TM-a和TM-ab是优势种类。我们还评估了补体在大鼠缺血性胃粘膜损伤模型中的作用。CVF和补体抑制剂K-76 COOH预处理可明显减轻再灌注后胃粘膜损伤，提示补体及其调节系统在胃肠道病理中可能起重要作用。