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

与缺血和各种中毒发病机制相关的新脂肪酸的鉴定及其在新诊断方法中的应用

基本信息

批准号：
12470107
负责人：
YOSHIDA Ken-ichi
金额：
$ 9.54万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

1）一氧化碳（CO）中毒相关的脂质过氧化和损伤的研究在一例亚急性CO中毒病例中，基底节、皮质和海马均出现坏死和凋亡，病灶的分布无法解释。在大鼠 CO 中毒模型中（90 分钟 CO 暴露，然后 2 天恢复），出现坏死，特别是在皮质下，有强烈的染色。过氧化脂质产物 4-羟基壬烯醛 (HNE) 在坏死区域的细胞核中减弱了坏死和 HNE 的产生。另外，通过新的测定系统，另一种脂质过氧化产物 7-羟基甾醇被证明可以减弱坏死区域的细胞核。暴露于 CO 后会增加低温减弱了 CO 诱导的 7-羟基甾醇生成，表明脂质过氧化参与了2）心肌梗死相关脂质过氧化和损伤的研究在大鼠心肌梗死模型中，HNE和TNF-α大幅升高，但缺血预处理减弱了这种升高。 IP：模拟梗塞前心绞痛的短暂缺血-再灌注周期，IP 减弱了 TNF-α 的生成。梗死心肌和活性氧相关转录因子 NFκB 的激活，众所周知，NFκB 会促进一氧化氮介导的细胞损伤和白细胞相关炎症。 3) CO 暴露对心肌缺血性细胞死亡的有益影响的研究-肌源性H9c2细胞。CO暴露通过MAP激酶/ERK途径减弱化学缺血诱导的H9c2细胞的坏死性死亡、活性氧生成和HNE形成。