Key Laboratory of Education Ministry on Traditional Chinese Medicine Resource and Compound Prescription, Hubei University of Chinese Medicine, Wuhan 430065, China.
Key Laboratory of Education Ministry on Traditional Chinese Medicine Resource and Compound Prescription, Hubei University of Chinese Medicine, Wuhan 430065, China.
Biomed Pharmacother. 2018 Mar;99:245-252. doi: 10.1016/j.biopha.2018.01.059.
The Lidanpaidu Prescription (LDP), a hospital preparation, composed of Chinese classical preparations, has been reported to have antiendotoxin, anticoagulant and other effects. However, its therapeutic effect on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and the mechanisms remain unclear. Therefore, we administered LPD pretreatment at different doses to examine the protective effects and mechanisms in LPS-induced AKI in mice. The kidney injury induced by LPS was assessed by histological examination. ELISA was used to detect the levels of inflammatory cytokines. The mRNA expression of the inflammatory genes IKKβ and TNF-α in kidney tissues was assessed by RT-PCR. Finally, Western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence laser confocal microscopy. The findings suggested that LDP significantly improved at 48 h animal survival (66.7%), compared with the LPS group (26.7%), determined by a Kaplan-Meier analysis. LDP attenuated the kidney histopathological changes induced by LPS and decreased the inflammatory cytokine levels in serum and renal tissue. Moreover, LDP markedly inhibited the expression of inflammatory genes and suppressed the activation of relevant proteins in the nucleus. In summary, these findings suggest that LDP reduces LPS-induced AKI via a mechanism related to the suppression of the NF-κB signaling pathway.
利胆排石片（LDP）是一种由中药制剂组成的院内制剂，具有抗内毒素、抗凝等作用。然而，其对脂多糖（LPS）诱导的急性肾损伤（AKI）的治疗作用及机制尚不清楚。因此，我们用不同剂量的 LDP 预处理，以研究其对 LPS 诱导的 AKI 小鼠的保护作用及机制。通过组织学检查评估 LPS 诱导的肾损伤。采用 ELISA 法检测炎性细胞因子水平。采用 RT-PCR 检测肾组织中炎性基因 IKKβ和 TNF-α的 mRNA 表达。最后，采用 Western blot 法检测 NF-κB 信号通路相关蛋白，并用免疫荧光激光共聚焦显微镜检测 NF-kB P65 的核转位。结果表明，LDP 可显著提高 LPS 诱导的 AKI 小鼠的 48 h 动物存活率（66.7%），与 LPS 组（26.7%）相比，差异有统计学意义（采用 Kaplan-Meier 分析）。LDP 可减轻 LPS 诱导的肾组织病理变化，降低血清和肾组织中炎性细胞因子水平。此外，LDP 可显著抑制炎性基因的表达，抑制相关蛋白在核内的激活。综上所述，这些结果提示 LDP 通过抑制 NF-κB 信号通路减轻 LPS 诱导的 AKI。
