南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (05): 598-.doi: 10.12122/j.issn.1673-4254.2019.05.16

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槲皮素通过抑制TLR4/NF-κB通路缓解脂多糖诱导的急性肾损伤

谭继翔，何进，秦文熠，赵林   

  • 出版日期:2019-05-20 发布日期:2019-05-20

Quercetin alleviates lipopolysaccharide-induced acute kidney injury in mice by suppressing TLR4/NF-κB pathway

  • Online:2019-05-20 Published:2019-05-20

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摘要： 目的分析槲皮素对脂多糖诱导小鼠急性肾损伤的保护作用，并初步探讨其机制。方法将40 只BALB/c小鼠随机分 为4 组：对照组（无脂多糖及槲皮素），脂多糖组（15 mg/kg 脂多糖），低剂量组（25 mg/kg 槲皮素+15 mg/kg 脂多糖），高剂量组 （50 mg/kg槲皮素+15 mg/kg脂多糖）。槲皮素予以胃灌注预处理，1次/d，连续3 d，对照组同时予以相同体积的生理盐水。最后 1次灌胃后1 h予以腹腔注射15 mg/kg的脂多糖，脂多糖干预24 h后结束实验，处死小鼠。观察小鼠肾脏组织病理变化和血肌 酐、尿素氮评估肾脏损伤情况，ELISA 法检测血清中TNF-α、IL-1β、IL-6 的表达情况，Western blot 检测肾脏胞浆中TLR-4、 MyD88、TRAF-6以及核内NF-κB p65蛋白的表达。结果槲皮素可以降低脂多糖诱导的急性肾损伤的肌酐、尿素氮水平以及肾 脏损伤的评分（P<0.05），降低血清中TNF-α、IL-1β、IL-6的表达（P<0.05），槲皮素抑制肾脏组织中TLR4、MyD88、TRAF-6及核 内NF-κB p65蛋白的表达（P<0.05）。结论槲皮素预处理可能通过抑制TLR4/NF-κB信号通路保护脂多糖诱导的小鼠急性肾损伤。

Abstract: Objective To investigate the protective effect of quercetin against lipopolysaccharide (LPS)- induced acute kidney injury (AKI) in mice and explore its mechanism. Methods Forty male BALB/c mice were randomly divided into control group (with saline treatment), 15 mg/kg LPS group, and quercetin-treated groups with intragastric quercetin treatment (once daily for 3 consecutive days) at low (25 mg/kg) and high (50 mg/kg) dose prior to 15 mg/kg LPS injection. LPS was administered by intraperitoneally injection 1 after the last gavage of quercetin. The mice were sacrificed 24 h after LPS injection for analysis of kidney pathologies, blood urea nitrogen (BUN) and creatinine levels; serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were detected by ELISA, and the expressions of Toll-like receptor-4 (TLR4), MyD88, TRAF-6 and NF-κBp65 in the kidney were detected by Western blotting. Results Quercetin significantly lessened renal pathologies, lowered BUN and creatinine levels (P<0.05) and inhibited TNF-α, IL-1β, and IL-6 production in mice with LPS-induced AKI (P< 0.05). Pretreatment with quercetin also significantly inhibited TLR4, MyD88, and TRAF-6 expressions and NF-κBp65 activation in the kidneys of the rats with LPS challenge (P<0.05). Conclusion Quercetin pretreatment can protect mice against LPSinduced AKI by inhibiting TLR4/NF-κB signaling pathway.