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Apopotosis Suppression in Ischemic Tolerance Phenomenon

缺血耐受现象中的细胞凋亡抑制

基本信息

批准号：
10670609
负责人：
KATAYAMA Yasuo
金额：
$ 1.22万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670609/
关键词：
ischemic tolerance delayed neuronal death hippocampus apoptosis

项目摘要

We investigated a pathogenetic role for expression in interleukin-1β converting enzyme (ICE) and interleukin-1β (IL-1β) in ischemic tolerance phenomenon. Male Mongolian gerbils were subjected to 5 min forebrain ischemia with or without 2 min sublethal ischemia 24 hours before the 5 min lethal ischemia. Animals were transcardially perfused using 4% paraformaldehyde at 1, 2, 3, 4, or 7 days after the lethal iuschemia, and paraffin-embedded coronal sections including hippocampus were cut on a microtome. Sections were stained with hematoxylin and eosin (HE) staining, and studied immunohistochemically using anti-serum against ICE or IL-1β. Furthermore TUNEL method was applied to the sections to evaluate neuronal DNA fragmentation in the hippocampal CA1 subfield. In the HE stained sections, marked reduction in number of hippocampal neurons was observed from 4 days after lethal ischemia, but the neuronal death was significantly suppressed by preconditioning. ICE immunoreactive neurons were observed from 2 to 4 days after lethal ischemia, although such neurons were scattered form 3 to 4 days in the preconditioned animals. IL-1β was strongly expressed from 4 days, but occasionally scattered in the preconditioned animals. Most of the IL-1β positive cells were microglia. TUNEL positive neurons were markedly increased from 3 days, although less observed in the preconditined animals. These suggest a role for apoptotic suppressive mechanisms in ischemic tolerance phenomenon.

本研究旨在探讨白细胞介素1β转换酶（ICE）和白细胞介素1β（IL 1β）在缺血耐受中的作用。雄性长爪沙鼠在5 min致死性脑缺血前24 h进行5 min的前脑缺血，并伴有或不伴有2 min的亚致死性脑缺血。在致死性缺血后1、2、3、4或7天，使用4%多聚甲醛经心脏灌注动物，并在切片机上切割石蜡包埋的冠状切片，包括海马。切片用苏木精和伊红（HE）染色，并使用抗ICE或IL-1β的抗血清进行化学染色研究。采用TUNEL法检测海马CA 1区神经元DNA断裂情况。在HE染色切片中，从致死性缺血后4天开始观察到海马神经元数量明显减少，但预处理明显抑制了神经元的死亡。致死性脑缺血后2 ~ 4天出现ICE免疫反应阳性神经元，而预处理后3 ~ 4天出现ICE免疫反应阳性神经元。IL-1β从第4天开始强烈表达，但在预处理的动物中偶见散在表达。IL-1β阳性细胞主要为小胶质细胞。TUNEL阳性神经元从第3天开始明显增加，但在预处理的动物中观察到较少。这些提示了凋亡抑制机制在缺血耐受现象中的作用。