Nerolidol Protects Against LPS-induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Signaling
Nerolidol Protects Against LPS-induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Signaling
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DOI：
10.1002/ptr.5770
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发表时间：
2017-03-01
影响因子：
7.2
通讯作者：
Guo, Minghao
中科院分区：
文献类型：
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作者：
Zhang, Lu;Sun, Dandan;Guo, Minghao
急性肾损伤（阿基）是一种重症监护综合征，导致肾功能急性下降，住院患者死亡率高达22%。橙花叔醇是几种精油的主要成分，具有各种药理学特性。本研究旨在研究橙花叔醇对脂多糖（LPS）诱导的阿基的潜在作用。橙花叔醇可剂量依赖性地减轻LPS所致大鼠肾脏病理损伤。橙花叔醇可显著降低LPS处理大鼠的血尿素氮和肌酐水平，并呈剂量依赖性。此外，橙花叔醇抑制LPS诱导的NRK-52 E大鼠近端肾小管细胞活力下降，这种作用具有浓度依赖性。橙花叔醇可显著抑制LPS诱导的大鼠TNF α和IL-β α的升高及LPS诱导的NRK-52 E细胞TNF α和IL-1 β mRNA的表达。橙花叔醇可抑制LPS诱导的大鼠肾脏和NRK-52 E细胞中Toll样受体4（TLR 4）表达、p65 NF-κ B B磷酸化和核转位。TLR 4和p65 NF-κ B的过表达显著抑制了Nerolidol诱导的LPS处理的细胞中TNF α和IL-1 κ表达的抑制以及细胞活力的增加。综上所述，我们发现橙花叔醇通过抑制TLR 4/NF-κ B信号通路发挥关键的抗炎作用，并保护LPS诱导的阿基。版权所有（C）2017约翰威利父子有限公司
Acute kidney injury (AKI) is a critical care syndrome, resulting in acute reduction of renal function and up to 22% mortality of hospitalized patients. Nerolidol is a major component in several essential oils that possesses various pharmacological properties. The present study aimed to investigate the potential effect of nerolidol on lipopolysaccharide (LPS)-induced AKI. Nerolidol dose-dependently reduced the pathological injuries of kidney induced by LPS in rats. Nerolidol significantly decreased the levels of blood urea nitrogen and creatinine in LPS-treated rats in a dose-dependent manner. In addition, nerolidol inhibited LPS-induced decrease of cell viability in NRK-52E rat proximal tubular cells, which effect was concentration dependent. Nerolidol notably inhibited the increase of TNF alpha and IL-beta a in LPS-treated rats and the mRNA expression of TNF alpha and IL-1 beta in LPS-treated NRK-52E cells. Nerolidol suppressed the increase of toll-like receptor 4 (TLR4) expression, phosphorylation and nuclear translocation of p65 NF-kappa B in kidneys of LPS-treated rats and LPS-treated NRK-52E cells. Overexpression of TLR4 and p65 NF-kappa B significantly suppressed nerolidol-induced inhibition of TNF alpha and IL-1 kappa expression and increase of cell viability in LPS-treated cells. In summary, we found that nerolidol played a critical anti-inflammatory effects through inhibition of TLR4/NF-kappa B signaling and protected against LPS-induced AKI. Copyright (C) 2017 John Wiley & Sons, Ltd.