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

在这个项目中，我们打算澄清在环境压力期间和之后体内一氧化氮的来源。主要研究结果总结如下。(1)建立了一氧化氮和8-羟基-2-脱氧鸟苷（8OHdG）在体内和体外实验中的测定系统。(2)一氧化氮含量为：尿液：127lmM，血浆：43.6，回肠：42.4，肝：28.3，脑：15.4。(3) LPS LPS诱导小鼠血浆NOx在注射后至少2 h升高。NOx升高持续至注射后24小时。IL-1 KO小鼠和HO-1活性抑制BALB/c小鼠均可抑制lps诱导的血浆NOx增加。(4)大鼠和小鼠脑缺血可引起脑下丘脑延迟性细胞死亡。缺血应激后2 ~ 4d，一氧化氮和8OHdG的表达增强。由于NOx和8OHdG的诱导与自由基氧（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)人脑血管损伤通常在原发事故发生数天后诱发血管痉挛发作，使患者的一般情况值得注意。在人体内施用环加氧酶抑制剂可显著减弱脑热疗，并抑制脑脊液中细胞因子、NOR和8OHdG的升高。在大脑受损的患者中，通过PGE途径产生的ROS似乎启动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下的机体氧化应激的良好标志。(7) 8OHdG/dG测量系统可用于评价人工化学物质的诱变性和生物毒性。

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.