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Molecular pathological study on vascular lesions due to ischemic heart diseases and related diseases

缺血性心脏病及相关疾病引起的血管病变的分子病理学研究

基本信息

批准号：
16390191
负责人：
YOSHIDA Ken-ich
金额：
$ 8.13万
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：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390191/
关键词：
Ishemia reperfusion Nitric oxide Reactive oxygen species Blood plow Lipid peroxidation Myocardial cell death Metabolic syndrome Inflammation 虚血性心疾患アポトーシスコネクシン不整脈

项目摘要

After short (<30 min) and long (>45 min) time of ischemia conferred by coronary artery occlusion of the rats, reperfusion caused dilatation and constriction of arterioles, respectively. The vascular diameter was correlated with phosphorylation of Akt and serine 1177 residue of eNOS. Reactive oxygen species (ROS) generation and PKC activation contribute to the vasoconstriction through inhibition of eNOS phosphorylation. In the blood of Lipopolysaccaride-injected rat, monocyte NADPH generate ROS, thereby promoting HNE production, as detected by the highly sensitive immunoassay that we have developed.We have developed a time-resolved fluoroimmunoassay for a lipid peroxide 4-hydroxynonenal (HNE), which is 100-fold more sensitive than conventional ELISA. By this assay, we found that a low dose bacterial lipo-polysaccharide (LPS) increased serum HNE, with a peak at 20 min. LPS increased HNE in vitro in the monocyte-enriched plasma, which was inhibited by a specific NADPH oxidase inhibitor. These data suggest that monocyte NADPH oxidase is involved in the lipid peroxidation (HNE formation) in the LPS-challenged rat.

大鼠冠状动脉结扎造成短时间(&lt；30min)和长时间(&gt；45min)缺血后，再灌流分别引起小动脉扩张和收缩。血管直径与Akt的磷酸化和eNOS的丝氨酸1177残基相关。活性氧物种(ROS)的产生和PKC的激活通过抑制eNOS的磷酸化参与血管收缩。在注射脂多糖的大鼠血液中，单核细胞NADPH产生ROS，从而促进HNE的产生，正如我们发展的高灵敏免疫分析方法所检测的那样。我们建立了一种时间分辨的荧光免疫分析方法，用于检测过氧化脂质4-羟基壬烯醛(HNE)，其灵敏度是常规ELISA法的100倍。通过本实验，我们发现低剂量的细菌脂多糖(LPS)可使血清HNE升高，在20min时达到峰值。脂多糖在体外增加单核细胞浓缩血浆中的HNE，这可被一种特定的NADPH氧化酶抑制剂抑制。这些结果提示单核细胞NADPH氧化酶参与了脂多糖激发的大鼠的脂质过氧化反应(HNE的形成)。

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Brief Regional Ischemic-reperfusion Enhances Propofol-induced Depression in Left Ventricular Function of in situ Rat Hearts.

短暂的局部缺血再灌注增强异丙酚诱导的原位大鼠心脏左心室功能抑制。

DOI：
发表时间：
2004
期刊：
Anesthesiology 101
影响因子：
0
作者：
上山敬司他;Nemoto K et al.;Nemoto K;Yukawa K;Yukawa K;Yukawa K et al.;Yukawa K et al.;Nemoto K et al.;Kuzumoto N et al.
通讯作者：
Kuzumoto N et al.

Estrogen replacement suppresses stress-induced cardiovascular responses in ovariectomized rats