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The role of arachidonic acid cascade in the development of delayed neuronal death

花生四烯酸级联在迟发性神经元死亡发展中的作用

基本信息

批准号：
01570802
负责人：
NAKAGOMI Tadayoshi
金额：
$ 1.22万
依托单位：
Teikyo University School of Medicine (1991)The University of Tokyo (1989-1990)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570802/
关键词：
cyclooxygenase lipoxygenase indomethacin delayed neronal death hippocampus gerbil immunohistochemistry prostaglandin 脳虚血

项目摘要

The role of arachdonic acid cascade in the develppent of delayed neuronal death following forebrain ischemia was investigated in the gerbils. First, immunohistochemical localization of prostaglandin(PG)F_<2alpha> synthesized during the recirculation phase following ischemia was studied. Frozen sebtions containing hippocampi were incubated with rabbit anti-PGF_<2alpha> serum and stained by the avidin-biotin-peroxidase complex method. In the control animals having sham operation, blood vessels were faintly stained with anti-PGF_<2alpha> serum. Less or no stain was found in neurons and glial cells. After recirculation, the experimental animals demonstrated marked positive staining for PGF_<2alpha> in blood vessels, neurons, especially hippocampal pyramidal neurons, and glial cells. Next, we examined the possibility that indomethain, a cyclooxygenase inhibiro, prevents ischemic delayed neuronal death in the gerbil hippocampus. Forebrain ischemia for 5 min was prduced by bilateral carotid occlusion. Animals received intraperitoneal injection of indomethacin(1, 2, 5 and 10mg/kg)30 min before ischemic insult. They were perfusion-fixed 7 days afere ischemic insult, and the neuronal density in the CA_1 sector was counted. Indomethacin at each dose significantly prevented delaye neuronal death in the hippocampal CA_1 sector. Effects of cyclooxygenase inhibior other than indomethacin and lipoxygenase inhibior delayed neuronal death were also examined in the same gerbil model. Piroxycam(10mg/kg)and Flurbiprofen(10mg/kg)ameliorated significantly delayed neuronal death. However, lipoxygenase inhibiotrs, AA801 and BW755C, did not ameliorated delayed neuronal death. Above results strongly suggest that cylooxygenase products may involved in the development of delayed neuronal death following forebrain ischemia in the ferels.

本文研究了花生四烯酸级联反应在沙土鼠前脑缺血后迟发性神经元死亡中的作用。首先，研究了缺血再循环期前列腺素（PG）F_2合成的免疫组织化学定位<2alpha>。用兔抗PGF_2血清孵育含鸡胚的冰冻切片<2alpha>，用亲和素-生物素-过氧化物酶复合物法染色。假手术对照组血管抗PGF_2血清染色较淡<2alpha>。神经元和胶质细胞染色较少或无染色。再灌流后，实验动物的<2alpha>血管、神经元，特别是海马锥体神经元和胶质细胞中PGF_2呈明显阳性染色。接下来，我们研究了吲哚美因（一种环氧合酶抑制剂）预防沙鼠海马缺血性迟发性神经元死亡的可能性。阻断双侧颈动脉造成前脑缺血5 min。缺血前30 min腹腔注射吲哚美辛1、2、5、10 mg/kg。缺血7天后行灌流固定，计数CA_1区神经元密度。吲哚美辛各剂量组均能显著预防海马CA_1区迟发性神经元死亡。环氧化酶抑制剂以外的吲哚美辛和脂氧合酶抑制剂的延迟性神经元死亡的影响也在同一沙土鼠模型进行了检查。吡罗昔康（10 mg/kg）和氟比洛芬（10 mg/kg）显著改善迟发性神经元死亡。然而，脂氧合酶AA 801和BW 755 C并没有改善迟发性神经元死亡。上述结果提示，环氧化酶产物可能参与了胎鼠前脑缺血后迟发性神经元死亡的发生。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

佐々木富男,中込忠好,桐野高明,田村晃,野口信,斉藤勇,高倉公朋: "インドメタシンによる海馬CA_1遅発性神経壊死の抑制" 医学のあゆみ. 145. 189-190 (1988)

Tomio Sasaki、Tadayoshi Nakagome、Takaaki Kirino、Akira Tamura、Makoto Noguchi、Isamu Saito、Kimitomo Takakura：“吲哚美辛对海马 CA_1 延迟性神经坏死的抑制”《医学史》145。189-190（1988）。