DEVELOPMENT OF NOVEL ASSAY SYSTEM FOR ANTI-ALLERGIC COMPOUNDS FROM NATURAL SOURCES AND APPLICATION

天然来源抗过敏化合物新型检测系统的开发及应用

基本信息

批准号：
15590106
负责人：
ISHIGURO Kyoko
金额：
$ 1.98万
依托单位：
MUKOGAWA WOMEN'S 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 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590106/
关键词：
Hen-egg white lysozyme Blood flow monitoring Allergy preventive medicines inducible NO synthase(iNOS)endothelin-1(ET-1)Anti-allergic assay system nitric oxide(NO)抗アレルギー NO 血流量 iNOS 血管内皮血栓症天然資源

项目摘要

We discovered a phenomenon in which the blood flow in vein microcirculation markedly decreases in response to hen-egg white lysozyme(HEL)-sensitization without any change in blood pressure. Using this blood flow decrease as a guide, we developed an in vivo assay method to search for substances, which can prevent allergies.We also investigated the mechanism of the blood flow decrease by the HEL-sensitization, using the inhibitors of chemical mediators and factors involved in the allergy or blood flow. Antagonists of histamine, serotonin and platelet activating factor(PAF) did not affect the blood flow decrease in response to HEL-sensitization. On the other hand, cyclooxygenase(COX)-1,COX-2, thromboxane(TX) A_2, endothelin-1(ET-1), prostacyclin (PGI_2) and granulocytic elastase(GE) as well as nitric oxide(NO) from inducible NO synthase(iNOS) were involved in the blood flow decrease. Thus, these substances might injure vascular endothelial cells, and cause a decrease in blood flow in vein microcirculation.Our method can be used to search for preventive agents against allergies involving NO,COX-1,2 and PGI_2. Knowledge of this mechanism enable us to develop an in vivo assay method to search for anti-allergic substances using the blood flow decrease caused by the HEL-sensitization.

我们发现了一种现象，即静脉微循环中的血流量因鸡蛋清溶菌酶（HEL）致敏而显着减少，但血压没有任何变化。以这种血流量减少为指导，我们开发了一种体内测定方法来寻找可以预防过敏的物质。我们还使用化学介质和因子的抑制剂研究了 HEL 致敏导致血流量减少的机制涉及过敏或血流。组胺、血清素和血小板活化因子 (PAF) 的拮抗剂不会影响 HEL 致敏反应中的血流量减少。另一方面，环氧合酶（COX）-1，COX-2，血栓素（TX）A_2，内皮素-1（ET-1），前列环素（PGI_2）和粒细胞弹性蛋白酶（GE）以及一氧化氮（NO）诱导型一氧化氮合成酶(iNOS)参与血流量减少。因此，这些物质可能会损伤血管内皮细胞，并导致静脉微循环血流量减少。我们的方法可用于寻找针对涉及NO、COX-1,2和PGI_2的过敏的预防剂。了解这一机制使我们能够开发一种体内测定方法，利用 HEL 致敏引起的血流量减少来寻找抗过敏物质。