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

在这个项目中，我们打算弄清楚在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)建立了体内和体外一氧化氮和8-羟基-2-脱氧鸟苷(8OHdG)的测定体系，(2)NO含量：尿液：127lmM，血浆：43.6，回肠：42.4，肝脏：28.3，脑：15.4。(3)注射内毒素后至少2小时，小鼠血浆NOx含量升高。NOx升高持续至注射后24小时。IL-1KO小鼠和抑制HO-1活性的BALB/c小鼠均能抑制脂多糖诱导的血浆NOx升高。(4)大鼠和小鼠脑缺血诱导脑下丘脑迟发性细胞死亡。缺血应激后2~4d，NOx和8OHdG的表达增强。由于NOx和8OHdG的诱导与自由基氧物种(ROS)的产生密切相关，这些数据似乎是神经细胞凋亡的一个很好的标记物。(5)人类大脑中的血管损伤通常在原发事故发生几天后诱发血管痉挛发作，从而使患者的一般情况变得有价值。环氧合酶抑制剂可显著降低脑温升高，抑制脑脊液中细胞因子、NOR和80HdG的升高。脑损伤患者通过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似乎都是环境应激下机体氧化应激的良好标志物。(7)8OHdG/dG测量系统对于评价人工化学物质的致突变性和生物毒性是非常有用的。

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.