Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, China.
Nephrology (Carlton). 2021 Jan;26(1):78-87. doi: 10.1111/nep.13781. Epub 2020 Sep 30.
Acute kidney injury (AKI) is a vital contributor to chronic kidney disease and limited therapeutic options are existed to preserve the renal injury. The research presented here investigated the protective effect of nodakenin against AKI and the underlying mechanism.
The effect of nodakenin was investigated in ischaemia reperfusion-induced renal injury (IRI) of AKI mice and hypoxia-treated primary renal tubular cells. Briefly, renal functions including creatinine and urea nitrogen were determined and mechanisms associated inflammation were investigated by the advantage of immunohistochemistry, western blot, RT-PCR and flow cytometry.
Deterioration of renal functions including and creatinine, urea nitrogen and tubular necrosis were observed in IRI-AKI model. In contrast, nodakenin strikingly alleviated the deterioration of creatinine, urea nitrogen and tubular necrosis when compared with IRI model. Moreover, nodakenin could significantly inhibit the expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α both in hypoxia-treated primary renal tubular cells and in AKI model. Mechanistic studies revealed that nodakenin dramatically suppressed the production of reactive oxygen species and subsequent NLPR3 inflammasome activation.
In summary, these findings provided a solid evidence base and a new drug option for the treatment of AKI.
急性肾损伤（AKI）是慢性肾脏病的重要病因，目前治疗方法有限，无法有效保护肾脏免受损伤。本研究旨在探讨芫花素对 AKI 的保护作用及其作用机制。
采用缺血再灌注诱导的 AKI 小鼠模型和缺氧处理的原代肾小管细胞，研究芫花素的作用。通过免疫组化、Western blot、RT-PCR 和流式细胞术等方法，探讨与炎症相关的机制。
在 IRI-AKI 模型中，肾功能包括肌酐、尿素氮和肾小管坏死均恶化。相比之下，与 IRI 模型相比，芫花素显著缓解了肌酐、尿素氮和肾小管坏死的恶化。此外，芫花素可显著抑制缺氧处理的原代肾小管细胞和 AKI 模型中促炎细胞因子白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α的表达。机制研究表明，芫花素可显著抑制活性氧的产生和随后 NLPR3 炎性小体的激活。
综上所述，这些发现为 AKI 的治疗提供了坚实的证据基础和新的药物选择。
