Expression of c-FOS and c-JUN proteins in the progression of brain damage

c-FOS 和 c-JUN 蛋白在脑损伤进展中的表达

• 批准号: 10671538
• 负责人: NAGATA Naoki
• 金额: $ 1.22万
• 依托单位: Tottori University
• 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-10671538/
• 关键词: hypoxic-ischemic brain damage; perinatal period; immature brain; 低酸素虚血性脳障害; 週生期

1.Using a hypoxic-ischemic brain damage model of neonatal rats, we gave rats two kinds of insult : a 90-min consecutive insult and repeated intermittent exposure for 10 minutes with 10 minute intervals, for a total of 90 minutes of exposure in 180 minutes while observing them for hypoxic-ischemic stress. First, we investigated the change in cerebral blood flow and nitric oxide (NO) during hypoxic-ischemic insult. NO was generated as cerebral blood flow decreased during the insult ; however, even after cerebral blood flow returned to control level during a break period, NO was still generated. The generation of NO increased again after the insult ended, suggesting some relationship to the occurrence of brain damage.2.The generation of inducible nitric oxide synthase (iNOS) and peroxynitrite caused by hypoxic-ischemic insult was examined. In addition, after the administration of S-methyl-isothiourea (SMT), a selective inhibitor of iNOS, we observed the degree of brain damage and the expression of 3-nitotyrosine (NT), an index of the generation of peroxynitrite. The expression of and iNOS proteins was observed 6-36 hours and 12-48 hours after the start of the insult, respectively. NT expressed mostly on the side of ischemia and reached its maximum 48 hours. On the other hand, with the administration of SMT, brain tissue damage decreased significantly, and the expression of NT was restrained.3.After the first insult., second insults were given at various intervals. As a result, second insults given while iNOS activity increased worsened brain damage. On the other hand, the expansion of the disorders was restrained by the administration of the iNOS inhibitor. These results suggested that, in the perinatal immature brain, the expression of iNOS caused by hypoxic-ischemic insult and increased production of peroxynitrite is related to the worsening of brain damage.

1.采用新生大鼠缺氧缺血性脑损伤模型，给予大鼠两种侮辱：连续90分钟侮辱和间隔10分钟重复间歇暴露10分钟，总共180分钟暴露90分钟，同时观察其缺氧缺血应激。首先，我们研究了缺氧缺血损伤期间脑血流量和一氧化氮（NO）的变化。损伤过程中脑血流量减少，产生一氧化氮（NO）；然而，即使在休息期间脑血流量恢复到控制水平后，仍然会产生NO。损伤结束后NO生成量再次增加，提示与脑损伤的发生有一定关系。2.检测缺氧缺血损伤引起的诱导型一氧化氮合酶(iNOS)和过氧亚硝酸盐的生成。此外，在给予iNOS选择性抑制剂S-甲基异硫脲（SMT）后，我们观察了脑损伤的程度以及过氧亚硝酸盐生成指标3-硝基酪氨酸（NT）的表达。分别在损伤开始后6-36小时和12-48小时观察iNOS和iNOS蛋白的表达。 NT主要在缺血侧表达，48小时达到最大值。另一方面，SMT给药后，脑组织损伤明显减轻，NT表达受到抑制。3.第一次损伤后，每隔不同时间间隔进行第二次损伤。结果，在 iNOS 活性增加的同时进行的第二次攻击会加剧脑损伤。另一方面，iNOS抑制剂的使用抑制了疾病的扩展。这些结果表明，在围产期未成熟的大脑中，缺氧缺血性损伤引起的iNOS表达和过氧亚硝酸盐的产生增加与脑损伤的恶化有关。

项目成果

長田 直樹: "反復低酸素虚血負荷による脳障害発生と一酸化窒素" 周産期学シンポジウム. 16巻. 31-35 (1998)

Naoki Nagata：“反复缺氧缺血负荷引起的脑损伤和一氧化氮”围产学研讨会第 16 卷 31-35 (1998)。

Ikeno, S.: "Immature Brain Injury via Peroxynitrite Production Induced by Inducible Nitric Oxyde Synthase after Hypoxia-Ischemia in Rat"J. Obstet. Gynecol. Res.. 26・3. in press (2000)

Ikeno, S.：“大鼠缺氧缺血后诱导型一氧化氮合酶引起的未成熟脑损伤”J. Obstet Res.. 26·3。