Li Dan, Li Bo, Rui Yixin, Xie Hongxiao, Zhang Xiumeng, Liu Rong, Zeng Nan
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.
Chengdu Hanpharm Pharmaceutical Co., Ltd, Pengzhou, Sichuan 611930, China.
Phytomedicine. 2022 May;99:154021. doi: 10.1016/j.phymed.2022.154021. Epub 2022 Feb 26.
Piperazine ferulate (PF) is widely used in chronic nephritis and nephrotic syndrome in clinic. PF can improve diseases related inflammation by inhibiting the activation of nuclear factor kappa-B (NF-κB) signal. Acute kidney injury (AKI) is usually associated with the occurrence and development of renal inflammation. However, the nephroprotective effect and anti-inflammatory mechanisms of PF on AKI are not clear.
This study aimed to investigate the nephroprotective effects of PF on gentamicin (GM) induced AKI in rats and its potential mechanisms.
Male Sprague Dawley (SD) rats were intraperitoneally injected with GM (100 mg/kg/day) with or without PF (50 and 100 mg/kg/day) for 7 consecutive days. In vitro, the NRK-52e cells were exposed to GM (7 mg/ml) with or without PF (62.5 μg/ml) treatment. The renal injury and cell damage were assessed subsequently.
Our findings showed that PF treatment can significantly improve renal function, reduce renal pathological changes, and attenuate inflammatory response in rats treated with gentamicin. Besides, PF could significantly reduce the cell damage and cellular inflammatory response. In terms of mechanisms, our study revealed that PF can evidently inhibit the activation of NF-κB and nod-like receptor family pyrin domain protein 3 (NLRP3) inflammasome. Meanwhile, it could down regulate the expressions of protein and gene of p-IKKα, p-IKKβ, p-p65, p65, p50, p105, NLRP3 and IL-1β.
Our findings showed that PF may improve inflammation by inhibiting the NF-κB/NLRP3 pathway, so as to attenuate AKI.
阿魏酸哌嗪（PF）在临床上广泛应用于慢性肾炎和肾病综合征。PF可通过抑制核因子κB（NF-κB）信号的激活来改善疾病相关炎症。急性肾损伤（AKI）通常与肾脏炎症的发生和发展有关。然而，PF对AKI的肾保护作用及抗炎机制尚不清楚。
本研究旨在探讨PF对庆大霉素（GM）诱导的大鼠急性肾损伤的肾保护作用及其潜在机制。
雄性Sprague Dawley（SD）大鼠连续7天腹腔注射GM（100mg/kg/天），同时或不同时给予PF（50和100mg/kg/天）。体外实验中，NRK-52e细胞分别用GM（7mg/ml）处理，同时或不同时给予PF（62.5μg/ml）。随后评估肾脏损伤和细胞损伤情况。
我们的研究结果表明，PF治疗可显著改善庆大霉素处理大鼠的肾功能，减轻肾脏病理变化，并减轻炎症反应。此外，PF可显著减少细胞损伤和细胞炎症反应。在机制方面，我们的研究表明，PF可明显抑制NF-κB和NOD样受体家族含pyrin结构域蛋白3（NLRP3）炎性小体的激活。同时，它可下调p-IKKα、p-IKKβ、p-p65、p65、p50、p105、NLRP3和IL-1β的蛋白和基因表达。
我们的研究结果表明，PF可能通过抑制NF-κB/NLRP3途径改善炎症，从而减轻急性肾损伤。
