银杏内酯A对LPS诱发肝细胞损伤的保护作用及机制

被引：3

作者：

姜璐 ^{[1
]}

王伟芹 ^{[1
]}

路士华 ^{[1
]}

高金柱 ^{[2
]}

曹志群 ^{[1
]}

机构：

[1] 山东中医药大学附属医院

[2] 中国中医科学院西苑医院

来源：

山东医药 | 2017年 / 09期

关键词：

肝细胞; 银杏内酯A; 脂多糖; 炎症; Toll样受体4; 核因子-κB;

D O I：

暂无

中图分类号：

R575 [肝及胆疾病];

学科分类号：

1002 ; 100201 ;

摘要：

目的探讨银杏内酯A(GA)对脂多糖(LPS)诱发肝细胞损伤的保护作用及可能机制。方法将大鼠肝细胞随机分为6组:正常组、LPS组、LPS+CLI-095组、LPS+GA 20μmol/L组、LPS+GA 10μmol/L组、LPS+GA20μmol/L+LY294002组。MTT法检测细胞活性,Western blotting法检测肝细胞Toll样受体4(TLR4)表达,检测肝细胞NF-κB活性[NF-κB p65、磷酸化-NF-κB p65(p-p65)、磷酸化-IκBα(p-IκBα)、NF-κB p65基因结合活性],检测培养液中炎症细胞因子IL-1β、IL-6、TNF-α水平。结果与正常组比较,LPS组肝细胞TLR4表达增加(P<0.05),NF-κB p65、p-p65、p-IκBα水平升高(P均<0.05),NF-κB p65基因结合活性增强(P<0.05),培养液中IL-1β、IL-6、TNF-α水平升高(P均<0.05),细胞活性降低(P<0.05)。与LPS组比较,GA剂量依赖性地抑制TLR4表达及NF-κB信号激活(P均<0.05),降低上述炎症因子的释放(P均<0.05),同时提高细胞活性(P<0.05)。TLR4抑制剂CLI-095干预后,LPS引起的肝细胞上述变化被阻断(P<0.05)。PI3K/Akt抑制剂LY294002可抵消GA对肝细胞的保护作用(P均<0.05)。结论 GA可抑制LPS引起的肝细胞炎症反应、提高细胞活性,其机制可能与抑制LPS引起的TLR-NF-κB信号过度激活有关;PI3K/Akt通路参与了LPS诱发肝细胞损伤过程。

引用

页码：28 / 30

页数：3

共 14 条

[1]

Tenuigenin exhibits protective effects against LPS-induced acute kidney injury via inhibiting TLR4/NF-κB signaling pathway[J] . Haiyan Fu,Zhansheng Hu,Xingwei Di,Qiuhong Zhang,Rongbin Zhou,Hongyang Du. &nbspEuropean Journal of Pharmacology . 2016

[2]

Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathway[J] . Hong Yao,Changsheng Hu,Lianhong Yin,Xufeng Tao,Lina Xu,Yan Qi,Xu Han,Youwei Xu,Yanyan Zhao,Changyuan Wang,Jinyong Peng. &nbspInternational Immunopharmacology . 2016

[3]

Berberine improves airway inflammation and inhibits NF-κB signaling pathway in an ovalbumin-induced rat model of asthma[J] . Zhenghao Li,Jie Zheng,Ning Zhang,Chengde Li. &nbspJournal of Asthma . 2016 (10)

[4]

去甲斑蝥素对LPS诱导的体外培养的肝细胞损伤的保护作用[J]. 周钧,王琴,王群伟,段文斌. 中南大学学报(医学版). 2012(03)

[5] 西红花酸对RAW264.7巨噬细胞TLR4/NF-κB信号通路的抑制作用及机制探讨 [J].

杨如会 ;

刘并进 .

山东医药, 2015, 55 (09) :15-17

[6]

Dioscin reduces lipopolysaccharideinduced inflammatory liver injury via regulating TLR4/My D88 signal pathway. Yao H,Hu C,Yin L,et al. International Journal of Immunopharmacology . 2016

[7] Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through STAT3-mediated pathway [J].

Zhao, Qiuping ;

Gao, Chuanyu ;

Cui, Zhifeng .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2015, 25 (02) :242-248

[8]

HO-1–STAT3 axis in mouse liver ischemia/reperfusion injury: Regulation of TLR4 innate responses through PI3K/PTEN signaling[J] . Bibo Ke,Xiu-Da Shen,Haofeng Ji,Naoko Kamo,Feng Gao,Maria Cecilia S. Freitas,Ronald W. Busuttil,Jerzy W. Kupiec-Weglinski. &nbspJournal of Hepatology . 2011 (2)

[9] Effects of hydroxyethyl starch on hepatic production of cytokines and activation of transcription factors in lipopolysaccharide-administered rats [J].

Lv, R ;

Zhou, W ;

Zhang, LD ;

Xu, JG .

ACTA ANAESTHESIOLOGICA SCANDINAVICA, 2005, 49 (05) :635-642

[10]

LPS-TLR4 pathway mediates ductular cell expansion in alcoholic hepatitis. Odena G,Chen J,Lozano JJ,et al. Science Reports . 2016

← 1 2 →