阿司匹林触发的脂氧素通过 TLR4/MyD88/NF-κB 通路保护脂多糖诱导的急性肾损伤。
Aspirin-Triggered Lipoxin Protects Lipopolysaccharide-Induced Acute Kidney Injury via the TLR4/MyD88/NF-κB Pathway.
机构信息
Department of Pediatrics, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China.
Department of Pediatrics, BenQ Medical Center, Nanjing Medical University, Nanjing, Jiangsu, China.
出版信息
Saudi J Kidney Dis Transpl. 2020 Sep-Oct;31(5):937-945. doi: 10.4103/1319-2442.301200.
The protective effect of aspirin-triggered lipoxin (ATL) on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanisms were explored. To induce acute renal injury, mice were treated with LPS. Concentration of serum creatinine (SCr) and blood urea nitrogen (BUN) was detected, and inflammatory cytokines and AKI biomarkers were determined by ELISA. The relative protein expression levels of TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB signal pathway was assessed by Western blot. Mice subjected to LPS (4 mg/kg) treatment exhibited AKI demonstrated by markedly increased SCr and BUN levels compared with controls (P <0.01). Treatment with ATL decreased SCr and BUN levels after LPS injection (P <0.01). AKI biomarkers, such as urine NGAL, KIM-1, netrin-1, and L-FABP levels, increased by LPS and were inhibited by ATL (P <0.01). ATL also reduced LPS-induced secretion of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and IL-8 (P <0.01). Furthermore, mice pretreated with ATL before exposure to LPS showed a reduction in TLR, MyD88, and p65 phosphorylation (P <0.01), which are the key factors of the TLR/MyD88/NF-κB signaling pathway. These results indicated that ATL had protective effects on renal function and showed amelioration of LPS-induced kidney injury. The mechanisms underlying the protective effects of ATL can be considered are related to attenuation of the TLR4/MyD88/NF-κB signaling pathway.
探讨了阿司匹林触发的脂氧素（ATL）对脂多糖（LPS）诱导的急性肾损伤（AKI）的保护作用及其可能的机制。为了诱导急性肾损伤，用 LPS 处理小鼠。通过 ELISA 检测血清肌酐（SCr）和血尿素氮（BUN）的浓度，并测定炎症细胞因子和 AKI 生物标志物。通过 Western blot 评估 TLR4/髓样分化因子 88（MyD88）/NF-κB 信号通路的相对蛋白表达水平。与对照组相比，用 LPS（4mg/kg）处理的小鼠表现出 AKI，其特征为 SCr 和 BUN 水平显著升高（P<0.01）。用 ATL 处理可降低 LPS 注射后 SCr 和 BUN 水平（P<0.01）。AKI 生物标志物，如尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子 1（KIM-1）、轴索导向因子 netrin-1 和脂肪细胞型脂肪酸结合蛋白（L-FABP）水平，因 LPS 而增加，并被 ATL 抑制（P<0.01）。ATL 还减少了 LPS 诱导的炎症细胞因子如肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6 和 IL-8 的分泌（P<0.01）。此外，用 LPS 处理前用 ATL 预处理的小鼠显示 TLR、MyD88 和 p65 磷酸化减少（P<0.01），这是 TLR/MyD88/NF-κB 信号通路的关键因素。这些结果表明 ATL 对肾功能具有保护作用，并显示出改善 LPS 诱导的肾损伤的作用。ATL 的保护作用的机制可以认为与 TLR4/MyD88/NF-κB 信号通路的衰减有关。
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