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ROLE OF PROSTAGLANDIN, THROMBOXANE AND RELATED AUTACOIDS

前列腺素、血栓烷和相关自体激素的作用

基本信息

批准号：
3257155
负责人：
PRASAD S KULKARNI
金额：
$ 20.08万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 1993-03-31
项目状态：
已结题

项目摘要

We have thus far determined the capacities of different ocular tissues such as conjunctiva, anterior uvea and cornea of various species (including monkey and human) to synthesize cyclooxygenase products: prostaglandins (PGs) PGE2, PGF2alpha, PGI2, PGD2 and thromboxane A2, and lipoxygenase products: monohydroxy acids and leukotrienes, from arachidonic acid (AA). In this proposal, we plan to study the roles these products play in the three phases (initiation, maintenance and termination) of ocular inflammation, especially the cellular inflammatory response. Their interaction with each other and other putative mediators such as histamine, bradykinin and chemotactic formylmethionyl polypeptide will be studied as well. In order to investigate the role of AA metabolites as either mediators or modulators, we will study the following using rabbits, cats and rats: 1) correlate the endogenous synthesis and release of PGs, thromboxane and leukotrienes with polymorphonuclear leukocytes (PMNs) infiltration of ocular fluids and tissues and breakdown of the blood-aqueous barrier during three phases of ocular inflammation. Three types of inflammation models will be used: a) paracentesis (no cellular response), b) endotoxin-induced uveitis (all inflammatory responses present) and c) corneal deepithelialization. 2) determine whether or not exogenous PGs and leukotrienes produce one or all inflammatory responses, administered alone or in combination with other autacoids to the normal eye. 3) determine whether or not drugs (steroidal and nonsteroidal), which interfere with AA metabolism at various enzymatic steps, affect one or all inflammatory responses in the three experimentally induced inflammation models outlined above. These studies will also be correlated with measuring the PMN count, leukotriene content and PG levels in tear fluids of volunteers with contact lens allergies. These studies will help in understanding the mechanism of mediators of ocular inflammation and development of new anti- inflammatory drugs.

到目前为止，我们已经确定了不同眼睛的能力，组织如结膜、前葡萄膜和角膜物种（包括猴子和人类）合成环氧合酶产物：前列腺素（PGs）PGE 2，PGF 2 α， PGI 2、PGD 2和血栓烷A2以及脂氧合酶产物：单羟基酸和白三烯，来自花生四烯酸（AA）。在本提案中，我们计划研究这些产品在三个阶段（启动、维持和终止）眼部炎症，特别是细胞炎症反应他们之间的相互作用和其他假定的介质如组胺、缓激肽和趋化因子甲酰基甲硫氨酰多肽也将被研究。为了研究AA代谢物的作用，介质或调节剂，我们将研究以下使用兔子、猫和老鼠： 1)与PG的内源性合成和释放相关，血栓素和白三烯与多形核白细胞（中性粒细胞）眼液和组织浸润以及血-房水屏障在眼的三个阶段炎症将使用三种类型的炎症模型： a）穿刺术（无细胞反应），B）内毒素诱导的葡萄膜炎 (all存在炎症反应）和c）角膜深石化作用 2)确定是否有外源性前列腺素和白三烯产生一种或所有炎症反应，单独给药或与其他自体类固醇联合应用于正常眼睛。 3)确定是否有药物（类固醇和非类固醇），其在各种酶促步骤中干扰AA代谢，影响三种炎症反应中的一种或全部上述实验诱导的炎症模型。这些研究也将与测量PMN相关泪液中的白细胞计数、白三烯含量和PG水平接触透镜过敏的志愿者。这些研究将有助于了解眼部炎症介质和新型抗炎症药物的开发消炎药