Kim Kiryeong, Hong Hyo-Lim, Kim Gyun Moo, Leem Jaechan, Kwon Hyun Hee
Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.
Department of Emergency Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.
Curr Issues Mol Biol. 2023 Aug 23;45(9):7027-7042. doi: 10.3390/cimb45090444.
Acute kidney injury (AKI) is a common complication of sepsis. Eupatilin (EUP) is a natural flavone with multiple biological activities and has beneficial effects against various inflammatory disorders. However, whether EUP has a favorable effect on septic AKI remains unknown. Here, we examined the effect of EUP on lipopolysaccharide (LPS)-evoked AKI in mice. LPS-evoked renal dysfunction was attenuated by EUP, as reflected by reductions in serum creatinine and blood urea nitrogen levels. LPS injection also induced structural damage such as tubular cell detachment, tubular dilatation, brush border loss of proximal tubules, and upregulation of tubular injury markers. However, EUP significantly ameliorated this structural damage. EUP decreased serum and renal cytokine levels, prevented macrophage infiltration, and inhibited mitogen-activated protein kinase and NF-κB signaling cascades. Lipid peroxidation and DNA oxidation were increased after LPS treatment. However, EUP mitigated LPS-evoked oxidative stress through downregulation of NPDPH oxidase 4 and upregulation of antioxidant enzymes. EUP also inhibited p53-mediated apoptosis in LPS-treated mice. Therefore, these results suggest that EUP ameliorates LPS-evoked AKI through inhibiting inflammation, oxidative stress, and apoptosis.
急性肾损伤（AKI）是脓毒症的常见并发症。灯盏乙素（EUP）是一种具有多种生物活性的天然黄酮，对各种炎症性疾病具有有益作用。然而，EUP对脓毒症相关性AKI是否具有有利作用仍不清楚。在此，我们研究了EUP对脂多糖（LPS）诱发的小鼠AKI的影响。EUP减轻了LPS诱发的肾功能障碍，血清肌酐和血尿素氮水平降低反映了这一点。注射LPS还会导致结构损伤，如肾小管细胞脱落、肾小管扩张、近端肾小管刷状缘丧失以及肾小管损伤标志物上调。然而，EUP显著改善了这种结构损伤。EUP降低了血清和肾脏细胞因子水平，防止巨噬细胞浸润，并抑制丝裂原活化蛋白激酶和NF-κB信号级联反应。LPS处理后脂质过氧化和DNA氧化增加。然而，EUP通过下调NADPH氧化酶4和上调抗氧化酶减轻了LPS诱发的氧化应激。EUP还抑制了LPS处理小鼠中p53介导的细胞凋亡。因此，这些结果表明，EUP通过抑制炎症、氧化应激和细胞凋亡改善了LPS诱发的AKI。
