[葛根素通过调节SIRT1/NF-κB信号通路减轻脂多糖诱导的小鼠急性肾损伤]
[Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway].
作者信息
Guo J, Zhang W, Liang P, Zhang L, Peng L, Min Y, Pan X, Yang Z, Deng H
机构信息
School of Basic Medical Sciences, Xiangnan University, Chenzhou 423000, China.
Department of Medical Administration, Chenzhou First People's Hospital, Chenzhou 423000, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Jul 20;43(7):1248-1253. doi: 10.12122/j.issn.1673-4254.2023.07.22.
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-) 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 ( < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF- and IL-1β ( < 0.01), enhanced renal expressions of TNF-, IL-1β and NF-κB p65(acetyl K310) ( < 0.01) and lowered renal expression of SIRT1 ( < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score ( < 0.01) and renal cell apoptosis rate ( < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF- and IL-1β ( < 0.01). Puerarin treatment significantly reduced TNF-, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue ( < 0.05) and increased SIRT1 expression by 17% ( < 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.
目的
探讨沉默信息调节因子1（SIRT1）/核因子κB（NF-κB）信号通路在介导葛根素抗脂多糖（LPS）诱导的急性肾损伤（AKI）中的作用。
方法
将15只BALB/C小鼠随机分为对照组、LPS组和葛根素治疗组。后两组小鼠腹腔注射LPS（5 mg/kg），随后连续3天每日注射生理盐水，或1小时后注射葛根素（25 mg/kg），然后连续3天每日注射。造模后第5天，取肾组织进行组织学观察及细胞凋亡检测。检测肾功能指标，包括尿素氮（BUN）、血清肌酐（Scr）和肾损伤分子1（KIM-1），以及肿瘤坏死因子（TNF-）和白细胞介素1β（IL-1β）水平，并检测肾组织中SIRT1和NF-κB-p65（乙酰化K310）的表达。
结果
腹腔注射LPS导致小鼠肾小球毛细血管明显扩张、充血，肾间质水肿，肾小管上皮细胞肿胀变形。LPS诱导的AKI小鼠模型还显示肾小管损伤评分和肾细胞凋亡显著增加（<0.01），血清BUN、Scr、KIM-1、TNF-和IL-1β水平升高（<0.01），肾组织中TNF-、IL-1β和NF-κB p65（乙酰化K310）表达增强（<0.01），肾组织中SIRT1表达降低（<0.05）。葛根素治疗有效减轻了LPS诱导的肾间质水肿和肾小管上皮细胞脱落，降低了肾小管损伤评分（<0.01）和肾细胞凋亡率（<0.01），并降低了血清BUN、Scr、KIM、TNF-和IL-1β水平（<0.01）。在小鼠模型中，葛根素治疗显著降低了肾组织中TNF-、IL-1β和NF-κB p65（乙酰化K310）的表达（<\u003c0.05），并使SIRT1表达增加了17%（<0.05）。
结论
葛根素可能通过调节SIRT1/NF-κB信号通路有效减轻LPS诱导的小鼠AKI。
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