Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury.
Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury.
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DOI：
10.1016/j.taap.2014.03.017
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发表时间：
2014-06-01
影响因子：
3.8
通讯作者：
Fu, Jian
中科院分区：
文献类型：
--
作者：
Chen, Jiao;Shetty, Sreerama;Zhang, Ping;Gao, Rong;Hu, Yuxin;Wang, Shuxia;Li, Zhenyu;Fu, Jian
血液中内毒素的存在可导致急性肾损伤（AKI）和感染性休克。溶解蛋白是一种内源性脂质介质，由二十二碳六烯酸衍生而来，据报道具有有效的抗炎作用。利用脂多糖（LPS）诱导的AKI小鼠模型，我们研究了阿司匹林触发的解决蛋白D1 （AT-RvD1）对炎症性肾损伤的影响。通过测量血尿素氮、血清肌酐和与肾小管损伤相关的形态学改变，LPS刺激后1小时给予AT-RvD1可保护小鼠免受肾损伤。肾脏中性粒细胞浸润减少表明炎症减轻，证明了其保护作用。AT-RvD1处理恢复了肾细胞连接蛋白claudin-4的表达，LPS刺激后该表达降低。AT-RvD1处理可抑制内毒素诱导的NF-κB活化，抑制lps诱导的肾组织ICAM-1和VCAM-1表达。此外，AT-RvD1治疗显著降低lps诱导的肾脏IL-6水平，阻断IL-6介导的信号通路，包括STAT3和ERK磷酸化。我们的研究结果表明，AT-RvD1在lps诱导的肾损伤中是一种有效的抗炎介质，并且AT-RvD1在内毒素血症期间具有治疗AKI的潜力。
The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.
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