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

1)与一氧化碳中毒相关的脂质过氧化和损伤的研究亚急性一氧化碳中毒患者基底节区、皮质区和海马区均出现坏死和凋亡性死亡。病变的分布不能用缺血来解释。在大鼠一氧化碳中毒模型中（暴露于一氧化碳90分钟后恢复2天），出现坏死，特别是在皮层下。坏死区细胞核内可见脂质过氧化产物4-羟基壬烯醛（HNE）的强烈染色。低温减轻了坏死和hne的产生。此外，通过新的检测系统，另一种脂质过氧化产物7-羟基甾醇在CO暴露后增加，低温降低了CO诱导的7-羟基甾醇的产生，表明脂质过氧化参与了CO中毒的发病机制，以及低温的临床应用可能性。2)心肌梗死与脂质过氧化及损伤的相关研究在心肌梗死大鼠模型中，HNE和TNF-α显著升高，而缺血预处理（IP：短暂缺血-再灌注周期）模拟梗死前心绞痛可使其减弱。IP减弱了梗死心肌中增强的TNF-α生成和活性氧相关转录因子NF κ B的激活，这是已知的促进一氧化氮介导的细胞损伤和白细胞相关炎症的因子。3) CO暴露对心肌源性H9c2细胞缺血性细胞死亡的有益作用研究。CO暴露可通过MAP激酶/ERK通路减弱化学缺血诱导的H9c2细胞的坏死死亡、活性氧生成和HNE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.