南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (7): 1248-1253.doi: 10.12122/j.issn.1673-4254.2023.07.22

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葛根素减轻LPS诱导的小鼠急性肾损伤:基于调节SIRT1/NF-κB信号通路

郭晶晶，张文龙，梁 飘，张龙军，彭凌音，闵钰琦，潘小珍，杨志英，邓华菲   

  1. 湘南学院基础医学院，郴州市第一人民医院医务部，湘南学院第一临床学院，湘南学院药学院，湖南 郴州 423000
  • 出版日期:2023-07-20 发布日期:2023-07-19

Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway

GUO Jingjing, ZHANG Wenlong, LIANG Piao, ZHANG Longjun, PENG Lingyin, MIN Yuqi, PAN Xiaozhen, YANG Zhiying, DENG Huafei   

  1. School of Basic Medical Sciences, Xiangnan University, Department of Medical Administration, Chenzhou First People's Hospital, First Clinical College of Xiangnan University, College of Pharmacy, Xiangnan University, Chenzhou 423000, China
  • Online:2023-07-20 Published:2023-07-19

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摘要： 目的 探讨SIRT1/NF-κB信号通路在葛根素抗脂多糖（LPS）所致急性肾损伤（AKI）中的作用及机制。方法 将15只BALB/C小鼠随机分为3组：对照组，LPS组，葛根素组。对照组小鼠腹腔注射生理盐水4 d；LPS组小鼠第1天注射LPS（5 mg/kg），随后注射生理盐水3 d，葛根素组小鼠第1天注射LPS（5 mg/kg）1 h后注射葛根素（25 mg/kg），继续注射葛根素3 d，第5天收集标本，观察小鼠肾组织形态变化，细胞凋亡情况；测定肾功能指标尿素氮（BUN）、肌酐（Scr）和肾损伤分子1（KIM-1）以及炎症因子肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）；检测肾组织SIRT1和NF-κB-p65（acetyl K310）的表达。结果 与对照组相比，LPS组小鼠肾小球毛细血管扩张、充血，肾间质水肿，肾小管上皮细胞肿胀，变形脱落，肾小管损伤评分增加（P<0.01），肾组织细胞凋亡率增加（P<0.01），血清中BUN、Scr、KIM-1、TNF-α和IL-1β升高（P<0.01），肾组织TNF-α、IL-1β mRNA 和NF-κB p65（acetyl K310）表达增加（P<0.01），而SIRT1表达降低了17%（P<0.05）。与LPS组相比，葛根素处理后肾间质水肿减轻，肾小管上皮细胞脱落不明显，肾小管损伤评分、肾组织细胞凋亡率降低（P<0.01），血清中BUN、Scr、KIM-1、TNF-α和IL-1β降低（P<0.01），肾组织TNF-α和IL-1β mRNA以及NF-κB p65（acetyl K310）表达降低了（P<0.05），SIRT1表达增加了17%（P<0.05）。结论 葛根素能够减轻LPS所致AKI，其机制可能与SIRT1/NF-κB信号通路有关。

关键词: 葛根素；急性肾损伤；脓毒症；SIRT1/NF-κB；炎症因子

Abstract: Objective To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Methods Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. Results Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P<0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1β (P<0.01), enhanced renal expressions of TNF-α, IL-1β and NF-κB p65(acetyl K310) (P<0.01) and lowered renal expression of SIRT1 (P<0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P<0.01) and renal cell apoptosis rate (P<0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1β (P<0.01). Puerarin treatment significantly reduced TNF-α, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue (P<0.05) and increased SIRT1 expression by 17% (P<0.05) in the mouse models. Conclusion Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.

Key words: puerarin; acute kidney injury; sepsis; SIRT1/NF-κB; inflammatory factors