Arachibonate cascade and physiological

(1)本文测定了高脂血症患者尿前列环素（PGI_2）代谢产物、血栓素A_2（TXA_2）代谢产物和8-异前列腺素（8-isoprostane）的水平。随着病情的加重，TXA_2/PGI_2的产生逐渐失衡，并与血脂水平有关。同时，二十碳五烯酸对TXA_2、PGI_2和8-异前列腺素的产生也有影响。糖尿病患者及妊娠期糖尿病、胎儿宫内发育迟缓等异常妊娠者TXA_2/PGI_2的失衡。(2)提示考克斯-2抑制剂在急性炎症模型中的抗炎作用是通过抑制考克斯-2产生PGE_2来实现的，而抑制PLA_2和考克斯-2的基因表达对地塞米松治疗中观察到的血浆渗出的抑制作用并不重要，考克斯-1而不是考克斯-2。 ...更多信息 在血管化模型中，VEGF通过调节PG的生成而促进血管化，同时也表明VEGF的诱导确实影响了血管化，我们建立了一个活细胞中考克斯活性的测定系统，发现考克斯除了具有考克斯活性外，还具有过氧化物酶活性，我们发现，只有考克斯-2利用内源性花生四烯酸和NO显着抑制考克斯-2的活性。用佛波酯诱导人巨核细胞白血病细胞CMK表达考克斯-1，并在CMK细胞中发现血小板中未发现的造血型PGD合成酶。TNF α可显著诱导小鼠成骨细胞MC 3 T3-E1中考克斯-2的表达，提示NF-κ B和NF IL-6在诱导过程中起转录因子的作用。(3)本文建立了白三烯B_4（LTB_4）的定量测定方法、LTB_4单克隆抗体放射免疫分析法、尿标本酶联免疫吸附测定法和LC/MS离子源微量测定法，发现哮喘患者尿中LTB_4和11 β-PGF_4水平显著高于<2a>健康人，阿司匹林诱发的哮喘患者尿中LTE_4水平显著升高，肺气肿患者尿中11 β-PGF_4水平显著升高<2a>，表明新型抗糖尿病药物曲格列酮对大鼠肥大细胞系RBL-2H_3产生LT有抑制作用。本研究还揭示了LTB_4受体的生物化学特性。LTB_4基因在CHO细胞中表达后，可引起腺苷酸环化酶活性的抑制，细胞内钙离子浓度的升高，从而影响细胞的活性。少

(1) We measured the urinary levels of prostacyclin (PGI_2) metabolites, thromboxane A_2 (TXA_2) metabolites, and 8-isoprostane in the patients with hyperlipidemia. Imbalance of the TXA_2/PGI_2 production was suggested in these patients with the progress of the disease, taking their serum lipids levels into consideration, It is also suggested that eicosapentaenoic acid administration influenced their TXA_2, PGI_2, and 8-isoprostane production. Moreover, imbalance of the TXA_2/PGI_2 production was observed in diabetics and in some cases with abnormal pregnancy such as gestational diabetes mellitus or intrauterine growth retardation.(2) It was indicated that the anti-inflammatory action in COX-2 inhibitors in acute inflammatory model was based on the inhibition of the PGE_2 production with COX-2, and that the suppression of the gene expression of PLA_2 and COX-2 were not so important for the suppression of the plasma exudation observed in the treatment with dexamethasone.Not COX-1 but COX … More -2 facilitated the vascularization through the regulation of the PG production in the vascularization model, It was also indicated that the induced VEGF actually influenced the vascularization in this model.We established a system for the measurement of the COX activity in lived cells, noticing that COX possesses the peroxidase activity in addition to the COX activity, With this system, we showed that only COX-2 utilized the endogenous arachidonic acid and that NO significantly suppressed the COX-2 activity. COX-1 was induced by phorbol ester in human megakaryoblast leukemia cells CMK.Hemopoietic type of the PGD synthetase, which was not identified in platelets, was identified in the CMK cells. COX-2 was significantly induced by TNFalpha in murine osteoblast cells MC3T3-E1, It was indicated that NF-kappaB and NFIL-6 played roles as the transcription factors in the course of the induction.(3) We established the quantitative methods of the leukotriene (LT) B_4 ; the radio immunoassay system using monoclonal antibody to LTB_4, the convenient enzyme-linked immunosorbent assay system using urinary samples, and the microdetermination system using LC/MS with ESI ion source.Patients with asthma showed significantly high levels of LTE_4 and 11beta-PGF_<2a> in urine compared with those with the healthy volunteers, Patients with aspirin-induced asthma showed greatly high LTE_4 levels in urine, Significantly high 11beta-PGF_<2a> levels were observed in the urine from the patients with pulmonary emphysema.We revealed that troglitazone, a novel antidiabetics, had LT-production suppressive action in the rat mast cell line RBL-2H3. We also revealed the biochemical aspects of the LTB_4 receptor that we succeeded in the cloning, When the LTB_4 gene expressed in CHO cells, it induced the inhibition of adenylate cyclase activity, increase in the concentration of the intracellular calcium, and it influenced to the wondering cell activity. Less