Identification of new fatty acids associated with pathogenesis of ischemia and various types of intoxication and its application to a new diagnostic method

1)一氧化碳中毒的脂质过氧化及损伤研究1例亚急性一氧化碳中毒大鼠的基底节、皮质和海马区均出现坏死性和凋亡性死亡。损伤的分布不能用缺血来解释。在大鼠一氧化碳中毒模型中(一氧化碳暴露90min后恢复2天)，出现坏死，尤其是皮质下。坏死区细胞核内有脂质过氧化产物--4-羟基壬烯醛(HNE)的强烈染色。亚低温可减轻HNE的生成和坏死。此外，新的检测系统显示，在CO暴露的低温下，另一种脂质过氧化产物7-羟基固醇增加，表明脂质过氧化参与了CO中毒的发病机制和低温临床应用的可能性。2)脂质过氧化和与心肌梗死相关的损伤的研究在心肌梗死大鼠模型中，HNE和肿瘤坏死因子-α显著增加，而这种增加可被模拟梗死前心绞痛的缺血预适应(IP：短暂缺血-再灌注周期)所减弱。3)一氧化碳暴露对心肌细胞缺血死亡的有利作用研究一氧化碳通过MAP/α途径抑制化学缺血诱导的H9c2细胞的坏死死亡、活性氧的产生和HNE的形成。3)一氧化碳暴露通过MAP/κ途径抑制化学缺血诱导的H9c2细胞的死亡、活性氧的产生和HNE的形成。

1) Research on lipid per-oxidation and injury associated with carbon monoxide (CO) poisoningThere were both necrotic and apoptotic death in the basal ganglia, cortex, and hippocampus in a subacute CO poisoning case. The distribution of the lesions could not be explained by ischemia. In a rat model of rat CO poisoning (90 min CO exposure followed by 2 days recovery), there was necrosis, particularly in the sub-cortex. There was intense staining of a lipid peroxide product, 4-hydoroxynonenal (HNE), in the nuclei of the necrotic area. Hypothermia attenuated the necrosis and HNE-generation. Additionally, by the new assay system, another lipid per-oxidation product 7-hydroxysterol was shown to be increased after CO-exposure Hypothermia attenuated the 7-hydroxysterol generation induced by CO, indicating the involvement of lipid per-oxidation in the pathogenesis of CO poisoning and the possibility of clinical application of hypothermia.2) Research on lipid peroxidation and injury associated with myocardial infarctionIn a rat model of myocardial infarction, HNE and TNF-α was greatly increased, while the increase was attenuated by ischemic preconditioning (IP : cycles of brief time of ischemia-reperfusion) that mimic the pre-infarction angina. IP attenuated the enhanced TNF-α generation in the infracted myocardium and the activation of reactive oxygen-associated transcription factor NF κ B, which is known to promote nitric oxide-mediated cell injury and leukocyte-associated inflammation.3) Research on the beneficial effect of CO exposure on ischemic cell death of cardio-myogenic H9c2 cells.CO exposure attenuated the necrotic death, reactive oxygen generation and HNE formation in the H9c2 cells induced by chemical ischemia through MAP kinase/ERK pathway.