基于NF-κB和Nrf2信号通路探讨槲皮素的护肝功效及其作用机理

Exploring Protective Effects and Mechanisms of Quercetin on Liver Injury Based on Both NF-κB and Nrf2 Signaling Pathways

为了研究槲皮素(Quercetin,QUE)对对乙酰氨基酚(Acetaminophen,APAP)造成的药物性肝损伤的保护作用及其护肝分子机制,将60只健康的BALB/c雄性小鼠随机等分为4组,2组为QUE高、低剂量干预组(100 mg/kg QUE和50 mg/kg QUE),2组为对照组和APAP肝损伤组。结果显示,与APAP肝损伤组相比,QUE干预能有效减轻APAP造成的肝病理性损伤,显著下调血清中丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)的活性、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的质量浓度,以及肝组织中丙二醛(MDA)的质量摩尔浓度;另外,QUE干预显著上调肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性和谷胱甘肽(GSH)的质量摩尔浓度,以及血清中抑炎因子白细胞介素-10(IL-10)的质量浓度;Western-blot结果显示,QUE干预显著上调核因子E2相关因子2(Nrf2)蛋白的表达,同时显著抑制核因子κB p65(NF-κB p65)蛋白的表达。结果表明,QUE的护肝功效不仅与激活Nrf2信号通路,加强机体的抗氧化应激水平相关,而且与抑制NF-κB信号通路,降低促炎因子释放密切相关,并呈现出量效特点。

To examine protective effect and potential mechanism of quercetin(QUE)on acetaminophen(APAP)-induced liver injury,sixty BALB/c mice were randomly divided into 4 groups,including high-and low-dose QUE groups(100 mg/kg,50 mg/kg),control group(physiological saline).The results showed that QUE administration could significantly ameliorate APAP-induced liver damage,reduce the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in sera,and simultaneously inhibited the level of malondialdehyde(MDA)in liver tissue.In addition,the activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),glutathione(GSH),and interleukin-10(IL-10)increased in QUE group compared with the APAP group.The results of Western-blotting showed that in QUE group,expression level of Nrf2 protein was markedly enhanced,but opposite result was observed in NF-κB protein expression.These findings suggested that QUE dose-dependently can alleviate APAP-induced liver injury via regulating Nrf2 and NF-κB signaling pathways.