文献类型：期刊文献

中文题名：基于TLR-4/NF-κB信号通路研究老鹳草素对四氯化碳致肝损伤小鼠的保肝作用

英文题名：The Liver-protecting Function and Mechanism of Geraniin on Mice with Acute Liver Injury Induced by Carbon Tetrachloride Based on TLR-4/NF-κB Signaling Pathway

作者：张帆[1];任真[2];高雅[1];曹后康[1];张可锋[1,2]

第一作者：张帆

机构：[1]桂林医学院,广西桂林541004;[2]甘肃中医药大学,甘肃兰州730000

第一机构：桂林医学院,广西桂林541004

年份：2018

卷号：41

期号：12

起止页码：2906

中文期刊名：中药材

外文期刊名：Journal of Chinese Medicinal Materials

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；PubMed;

基金：广西八桂学者专项(桂财教函[2017]143号);甘肃省第八批科研计划项目(1508RJZA008).

语种：中文

中文关键词：老鹳草素;急性肝损伤;抗氧化;抗炎;TLR-4/NF-κB信号通路

外文关键词：Geraniin;Acute liver injury;Anti-oxidation;Anti-inflammation;TLR-4/NF-κB signaling pathway

摘要：目的:研究老鹳草素对四氯化碳(CCl_4)致急性肝损伤小鼠的保护作用,并探索其作用机制。方法:将60只小鼠随机分为正常对照组、模型组、水飞蓟宾(180 mg/kg)阳性对照组及老鹳草素低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组,连续灌胃给药10 d。末次给药2 h后,除正常对照组外,其余各组腹腔注射0.1%CCl_4花生油溶液(10 mL/kg)建立CCl_4致小鼠急性肝损伤模型。16 h后,收集血清和肝组织。生化法测定血清ALT、AST、ALP、TBIL、γ-GT、MDA、T-SOD、GSH-Px水平;ELISA法检测肝组织中TNF-α、IL-1β、IL-6含量;Western-blot检测肝组织中TLR-4、NF-κB蛋白表达;HE染色观察肝组织病理学变化。结果:与模型组比较,老鹳草素能显著降低肝损伤小鼠血清ALT、AST、ALP、TBIL、γ-GT、MDA水平,显著升高血清T-SOD、GSH-Px活性,显著降低肝组织中TNF-α、IL-1β、IL-6含量和TLR-4、NF-κB蛋白表达(P<0.05或P<0.01);HE染色结果显示其对肝组织损伤有明显的改善作用。结论:老鹳草素对CCl_4制备的急性肝损伤小鼠具有显著的保护作用,其作用机制可能与抗炎、抗氧化及调控TLR-4/NF-κB信号通路有关。
Objective:To explore the protective effects and its mechanism of the Geraniin on mice with acute liver injury induced by carbon tetrachloride(CCl4).Methods:Sixty mice were randomly divided into normal group,model group,positive control group(silybin:180 mg/kg)and Geraniin low-(50 mg/kg),middle-(100 mg/kg)and high-dose group(200 mg/kg).All the mice were continuoously given the drug by gavage once a day for 10 d.Two hours later after the last administration,the mice except the normal group were injected intraperitoneally with 0.1% CCl4 peanut oil solution(10 mL/kg)to induce the acute liver injury model.16 h later,the eye balls of mice were removed to take blood,and all mice were sacrificed to collect samples of liver.Biochemical method was used to detect the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatasetotal(ALP),total bilirubin(TBIL),γ-glutamyl transpeptidase(γ-GT),malondialdehyde(MDA),superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)in serum.The contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in hepatic tissue were detected by ELISA assay,and expressions of TLR-4 and NF-κB proteins were detected by Western blot.HE staining was used to observe the pathological changes of liver tissue.Results:Compared with the model group,Geraniin could reduce the levels of ALT,AST,ALP,TBIL,γ-GT and MDA in serum of mice with liver damage,increase the activities of T-SOD and GSH-Px,meanwhile significantly inhibite the contents of TNF-α,IL-1β,IL-6 and expressions of TLR-4 and NF-κB proteins in liver tissues(P<0.05 or P<0.01).The results of HE staining showed that acute liver injury of mice was improved to different degrees obviously by Geraniin.Conclusion:Geraniin has obvious protective effective on acute liver injuries induced by CCl4 in mice.The mechanism may be related to anti-inflammation,anti-oxidation and the regulation of TLR-4/NF-κB signaling pathway.