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

1.采用新生大鼠缺氧缺血性脑损伤模型，对大鼠进行90分钟连续损伤和10分钟间隔10分钟的反复间歇性暴露，180分钟内共暴露90分钟，观察其缺氧缺血性应激。首先，我们研究了缺氧缺血性损伤时脑血流量和一氧化氮（NO）的变化。损伤时脑血流量减少产生NO；然而，即使在休息期间脑血流量恢复到控制水平后，仍会产生NO。侮辱结束后NO的生成再次增加，提示与脑损伤的发生有一定关系。研究了缺氧缺血性损伤诱导型一氧化氮合酶（iNOS）和过氧亚硝酸盐的生成。此外，在给予选择性iNOS抑制剂s -甲基异硫脲（SMT）后，我们观察了脑损伤程度和3-硝基酪氨酸（NT）的表达，NT是过氧亚硝酸盐生成的指标。分别于损伤开始后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，在缺血后48小时达到最大值。另一方面，随着SMT的施用，脑组织损伤明显减轻，NT的表达受到抑制。在第一次侮辱之后。每隔一段时间，就会有第二次侮辱。结果，当iNOS活动增加时，第二次侮辱加重了脑损伤。另一方面，iNOS抑制剂的使用抑制了疾病的扩展。这些结果提示，在围产期未成熟脑中，缺氧缺血性损伤引起的iNOS表达和过氧亚硝酸盐生成增加与脑损伤加重有关。

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.