抗炎吡喃查尔酮衍生物通过抑制 TLR4/NF-κB 通路减轻 LPS 诱导的急性肾损伤。

Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Pathway.

机构信息

Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.

出版信息

Molecules. 2017 Oct 10;22(10):1683. doi: 10.3390/molecules22101683.

Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively. Compound was orally administrated at a dose of 25 mg/kg/day for 5 days before LPS (10 mg/kg) intraperitoneal injection. Cells were pretreated with 25 μg/mL for 30 min before LPS (1 μg/mL) treatment. Pretreatment with markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1β, IL-6, and TNF-α both in renal tissue of AKI mice and in the LPS-stimulated HK-2 cell culture medium were reduced by treatment ( < 0.05). The results of immunohistochemistry staining showed that reduced the expression of NF-κB p65 in kidneys. Similarly, decreased the LPS-induced levels of NF-κB p65 and TLR4 proteins in kidneys and HK-2 cells. These data demonstrated that a potent pyranochalcone derivative, , exhibited renoprotective effect against LPS-induced AKI, which was associated with anti-inflammatory activity by inhibiting the TLR4/NF-κB pathway.

治疗脓毒症急性肾损伤（AKI）的效果仍不尽如人意，尽管抗炎治疗对脓毒症引起的 AKI 有益。是从天然吡喃查尔酮衍生而来的，在佐剂性关节炎中表现出很强的抗炎活性。在这项研究中，我们旨在研究对脂多糖（LPS）诱导的 AKI 的肾保护作用及其潜在机制。分别用 LPS 处理 C57BL/6 小鼠和人肾近端小管细胞系（HK-2 细胞）。在 LPS（10mg/kg）腹腔注射前，用 25mg/kg/天的剂量经口给予化合物 5 天。用 25μg/mL 的预处理细胞 30 min，然后用 LPS（1μg/mL）处理。预处理明显减轻了 LPS 诱导的 AKI 中的肾小管损伤和肾功能障碍。治疗（<0.05）降低了 AKI 小鼠肾组织和 LPS 刺激的 HK-2 细胞培养物中 IL-1β、IL-6 和 TNF-α 的表达。免疫组织化学染色结果表明，在肾脏中减少了 NF-κB p65 的表达。同样，降低了肾脏和 HK-2 细胞中 LPS 诱导的 NF-κB p65 和 TLR4 蛋白水平。这些数据表明，一种有效的吡喃查尔酮衍生物对 LPS 诱导的 AKI 具有肾保护作用，其通过抑制 TLR4/NF-κB 通路发挥抗炎作用。