Oxidative stress and coronary artery lesion in Kawasaki disease

Nrf2对抗氧化基因的表达至关重要。氧化应激在川崎病（KD）冠状动脉炎（CA）发展中的参与尚不清楚。我们在干酪乳杆菌细胞壁提取物（LCWE）诱导的小鼠KD模型中测试了Nrf2在小鼠体内的破坏是否会导致CA加重。6周龄雄性Nrf2敲除型（KO）和野生型（WT）小鼠分别注射PBS或300ug LCWE。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Ho-1和NQO1 mRNA表达降低。与我们的假设相反，KO小鼠表现出较轻的CA。KO小鼠的血清细胞因子水平，如TNFalpha， il1 β， IL6和MCP1低于WT小鼠。KO小鼠脾脏中凋亡细胞增多。这些结果表明，尽管Nrf2诱导抗氧化基因（益处），但它抑制炎症细胞的凋亡，导致KD患者CA（风险）加剧。

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.