Panaxadiol Saponin and Dexamethasone Improve Renal Function in Lipopolysaccharide-Induced Mouse Model of Acute Kidney Injury.
Panaxadiol Saponin and Dexamethasone Improve Renal Function in Lipopolysaccharide-Induced Mouse Model of Acute Kidney Injury.
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人参二醇皂苷和地塞米松改善脂多糖诱导的急性肾损伤小鼠模型的肾功能
DOI：
10.1371/journal.pone.0134653
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Chen Y;Du Y;Li Y;Wang X;Gao P;Yang G;Fang Y;Meng Y;Zhao X
急性肾损伤（AKI）是全身炎症反应综合征（SIRS）的一种严重并发症，死亡率较高。先前的研究表明，人参二醇皂苷（PDS）和地塞米松具有相似的抗炎特性，并能保护脂多糖（LPS）诱导的脓毒症休克大鼠的心肺功能。在本研究中，我们探讨了PDS或地塞米松在改善LPS诱导的AKI小鼠肾功能方面是否具有相似的作用。
接受LPS（10mg/kg）处理的小鼠出现了AKI，表现为与对照组相比血尿素氮和肌酐水平显著升高（P<0.01）。然而，PDS和地塞米松对肾功能有相似的逆转作用，例如与LPS组相比，血清肌酐和血尿素氮水平降低（P<0.05）。PDS通过抑制NF - κB信号通路、下调诱导型一氧化氮合酶蛋白表达水平以及抑制氧化应激，减少了肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的产生和释放。在大多数抗AKI机制中，PDS和地塞米松相似，但PDS在抑制TNF产生、促进超氧化物歧化酶（SOD）活性以及抑制IKB磷酸化方面表现更佳。此外，在PDS和地塞米松治疗组中，核糖皮质激素受体表达显著增强。需要进一步研究以确定PDS是否能与糖皮质激素受体结合进入细胞核。
本研究表明，PDS和地塞米松对肾功能有相似的逆转改善作用，在脓毒症诱导的AKI治疗中具有潜在的应用前景。
Background Acute kidney injury (AKI) is a serious complication of systemic inflammatory response syndrome (SIRS), which has a high mortality rate. Previous studies showed that panaxadiol saponin (PDS) and Dexamethasone have similar anti-inflammatory properties and protect cardiopulmonary function in lipopolysaccharide (LPS)-induced septic shock rats. In the present study, we investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice. Methods and Results Mice subjected to LPS (10 mg/kg) treatment exhibited AKI demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P<0.01). However, PDS and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P<0.05). PDS decreased the production and release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by inhibiting the NF-κB signaling pathway, down-regulating inducible nitric oxide synthase protein expression levels and inhibiting oxidative stress. In most anti-AKI mechanisms, PDS and dexamethasone were similar, but PDS are better at inhibition of TNF production, promote SOD activity and inhibition of IKB phosphorylation. In addition, nuclear glucocorticoid receptor expression was markedly enhanced in PDS and Dexamethasone treatment groups. Further research is required to determine whether PDS can combine with the glucocorticoid receptor to enter the nucleus. Conclusion This study demonstrated that PDS and dexamethasone have similar reverse amelioration for renal functions, and have potential application prospects in the treatment of sepsis-induced AKI.