权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SOURCE OF NITRIC OXIDES IN THE BODY DURING AND AFTER ENVIRONMENTAL STRESS

环境压力期间和之后体内一氧化氮的来源

基本信息

批准号：
09557007
负责人：
TAKAKI Atsushi
金额：
$ 8.06万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

In this project, we intended to clarify the sourcer of nitric oxides in the body during and after environmental stresses. Main results are summarized as follows.(1) We have established the assay system for measurement of both nitric oxides and 8-hydroxy-2-deoxgunaosin (8OHdG) in in vivo and in vitro experiment.(2) The contents of nitric oxides was as follows ; Urine : 127lmM, Plasma : 43.6, Ileum : 42.4, Liver : 28.3, Brain : 15.4.(3) LPS ip injection induced plasma NOx increased at least two hour after injection in mice. And NOx elevation was continued until 24 hour after the injection. Both IL-1 KO mice and inhibition of HO-1 activity in BALB/c mice suppressed the LPS-induced plasma NOx increase.(4) Brain ischemia in rat and mouse induced delayed cell death in the hypocampus in the brain. The expression of the NOx and 8OHdG were enhanced 2-4days after the ischemia stress. Since induction of NOx and 8OHdG were closely related to production of radical oxygen species (ROS), these data seems to be a good marker for apoptosis of the neural cells.(5) Vascular damages in the human brain usually induces the attack of vasospasum several days after the primary accident, then make the general condition of the patient worth. Administration of the cyclo-oxygenase inhibitor significantly in human attenuated the hyperthermia of the brain, and suppressed the elevation of the cytokines, NOR, and 8OHdG in cerebrospinal fluid. Production of the ROS via PGE pathway in patients damaged in the brain seems to initiate the catastrophe of the host-defensive functions.(6) NOx content ; was positively correlated to the 8OHdG contents in urine. Both NOx and 8OHdG seems to be a good marker for the oxidative stress in the body exposed to the environmental stress.(7) The measurement system for 8OHdG/dG was very useful for evaluation of mutagenesis and biological toxicity of artificial chemical substances.

在这个项目中，我们打算澄清环境压力期间和之后体内一氧化氮的来源。主要结果如下：(1)建立了体内外实验测定一氧化氮和8-羟基-2-脱氧古那红(8OHdG)的测定体系。(2)一氧化氮含量如下：尿液：127lmM，血浆：43.6，回肠：42.4，肝脏：28.3，脑：15.4。(3)在小鼠中注射LPS后至少两小时，腹膜内注射诱导血浆NOx增加。 NOx升高持续到注射后24小时。 IL-1 KO小鼠和BALB/c小鼠中HO-1活性的抑制均抑制了LPS诱导的血浆NOx增加。(4)大鼠和小鼠的脑缺血诱导了脑下丘脑中的延迟性细胞死亡。缺血应激后2-4天NOx和8OHdG的表达增强。由于NOx和8OHdG的诱导与自由基氧簇（ROS）的产生密切相关，这些数据似乎是神经细胞凋亡的良好标志。（5）人脑血管损伤通常会在原发事故数天后诱发血管痉挛发作，从而使患者的总体状况变得值得。给予人类环加氧酶抑制剂可显着减弱大脑的高热，并抑制脑脊液中细胞因子、NOR 和 8OHdG 的升高。大脑受损的患者通过 PGE 途径产生 ROS 似乎引发了宿主防御功能的灾难。(6) NOx 含量；与尿中8OHdG含量呈正相关。 NOx和8OHdG似乎都是暴露于环境应激的体内氧化应激的良好标记。(7)8OHdG/dG的测量系统对于评估人工化学物质的诱变和生物毒性非常有用。