Oxidative stress and coronary artery lesion in Kawasaki disease

NRF2对抗氧化基因的表达是必不可少的。氧化应激在川崎病(KD)冠状动脉动脉炎(CA)发病中的作用尚不清楚。我们测试了Nrf2在小鼠体内的破坏是否导致干酪乳杆菌细胞壁提取物(LCWE)诱导的KD小鼠模型中CA的加重。6周龄雄性Nrf2基因敲除(KO)和野生型(WT)小鼠分别注射PBS和300ug的LCWE。分别于用药后2周和4周评估CA的严重程度。KO小鼠体内包括HO-1和NQO1在内的抗氧化基因的mRNA表达降低。与我们的假设相反，KO小鼠表现出不那么严重的CA。KO组小鼠血清细胞因子水平明显低于WT组小鼠。KO小鼠脾细胞凋亡数增加。这些结果表明，尽管Nrf2诱导了抗氧化基因(Benefit)，但它抑制了炎症细胞的凋亡，导致了KD患者CA的加重(Risk)。

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.