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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）中毒致脂质过氧化损伤的研究1例亚急性CO中毒患者的基底节、皮质和海马均出现坏死和凋亡性死亡。缺血不能解释病变的分布。在大鼠CO中毒的大鼠模型中（90分钟CO暴露，随后2天恢复），有坏死，特别是在皮质下。在坏死区域的细胞核中，脂质过氧化物产物4-羟基壬烯醛（HNE）染色强烈。低温可减轻坏死和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-羟基甾醇被证明在CO暴露后增加。低温减弱了CO诱导的7-羟基甾醇的产生，提示脂质过氧化参与了CO中毒的发病机制，并提示了低血糖症临床应用的可能性。心肌梗死后脂质过氧化及损伤的研究在大鼠心肌梗死模型中，HNE和TNF-α明显升高，而缺血预处理可抑制其升高（IP：短暂缺血-再灌注时间的循环），其模拟梗塞前心绞痛。IP减弱了梗死心肌中TNF-α的产生和活性氧相关转录因子NF κ B的活化，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。3）研究CO暴露对心肌源性H9 c2细胞缺血性细胞死亡的有益作用。MAP激酶/ERK通路介导化学性缺血诱导H9 c2细胞活性氧产生和HNE形成。