Oxidative stress and coronary artery lesion in Kawasaki disease

川崎病的氧化应激与冠状动脉病变

• 批准号: 23791195
• 负责人: SUGANUMA EISUKE
• 金额: $ 2.33万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791195/
• 关键词: 川崎病冠動脈炎; LCWE; 酸化ストレス; Nrf2遺伝子; Keap1遺伝子; 川崎病; アポトーシス

Nrf2 is essential to the expression of antioxidant genes. Involvement of oxidative stress in the development of coronary arteritis(CA) in Kawasaki disease(KD) remains unknown. We have tested whether the disruption of Nrf2 in mice causes exacerbated CA in a murine model of KD induced by Lactobacillus casei cell wall extract(LCWE). Six week-old male Nrf2 knockout(KO) and wild type (WT) mice were injected with either PBS or 300ug of LCWE. Two and 4 weeks after LCWE administration, severity of CA was assessed. KO mice had decreased mRNA expression of antioxidant genes, including Ho-1 and NQO1. In contrast to our hypothesis, KO mice showed less severe CA. Serum cytokine levels such as TNFalpha, IL1beta, IL6 and MCP1 were lower in KO than WT mice. Spleen from KO mice exhibited increased number of apoptotic cells. These results suggest that, although Nrf2 induces antioxidant genes (benefit), it suppresses apoptosis of inflammatory cells, leading to exacerbation of CA (risk) in KD.

nrf 2对抗氧化基因的表达至关重要。氧化应激在川崎冠状动脉炎（CA）发生中的作用尚不清楚。我们已经测试了在小鼠中Nrf 2的破坏是否导致由干酪乳杆菌细胞壁提取物（LCWE）诱导的KD的鼠模型中CA加剧。用PBS或300 ug LCWE注射六周龄雄性Nrf 2敲除（KO）和野生型（WT）小鼠。LCWE给药后2周和4周，评估CA的严重程度。KO小鼠抗氧化基因的mRNA表达降低，包括Ho-1和NQO 1。与我们的假设相反，KO小鼠表现出不太严重的CA。KO小鼠的血清细胞因子水平（如TNF α、IL 1 β、IL 6和MCP 1）低于WT小鼠。KO小鼠的脾脏表现出凋亡细胞数量增加。这些结果表明，尽管Nrf 2诱导抗氧化基因（益处），但它抑制炎症细胞的凋亡，导致KD中CA的恶化（风险）。

项目成果

Nrf遺伝子欠損マウスはLCWE誘導性冠動脈炎を抑制する

Nrf 基因缺陷小鼠抑制 LCWE 诱导的冠状动脉炎症

• 发表时间: 2014
• 作者: 菅沼栄介;松田晋一;中村英明;関根佳織;新村文男;望月博之
• 通讯作者: 望月博之