文献类型：期刊文献

中文题名：龙胆苦苷对非酒精性脂肪肝TLR-4/NF-κB和AMPK/Nrf2通路的影响

英文题名：The effect of gentiopicroside on TLR-4/NF-κB and AMPK/Nrf2 in non-alcoholic fatty liver disease

作者：许琼梅[1];高雅[1];李梓萌[1];韦日明[1];马晓辉[2];晋玲[2];张可锋[1]

第一作者：许琼梅

机构：[1]桂林医学院药学院,桂林5410041;[2]甘肃中医药大学药学院,兰州730000

第一机构：桂林医学院药学院,桂林5410041

年份：2020

卷号：32

期号：10

起止页码：1652

中文期刊名：天然产物研究与开发

外文期刊名：Natural Product Research and Development

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家自然科学基金(81860673);广西八桂学者专项(2017143)。

语种：中文

中文关键词：龙胆苦苷;非酒精性脂肪肝;氧化应激;炎症反应;TLR-4/NF-κB通路;AMPK/Nrf2通路

外文关键词：gentiopicroside;non-alcoholic fatty liver;oxidative stress;inflammatory response;TLR-4/NF-κB pathway;AMPK/Nrf2 pathway

摘要：探讨龙胆苦苷(GPS)对非酒精性脂肪肝(NAFLD)大鼠的保护作用及TLR-4/NF-κB和AMPK/Nrf2通路的影响。将60只SD大鼠随机分为正常组、模型组、二甲双胍组(200 mg/kg)和GPS高、中、低剂量组(120、60、30 mg/kg)。正常组给予标准饲料,其余各组给予高脂饲料饲养14周,建立大鼠NAFLD模型。生化法检测肝功能、氧化应激和脂质积累情况,酶联免疫吸附试验(ELISA)检测胰岛素抵抗和炎症因子水平,蛋白免疫印迹实验(Western blot)检测大鼠肝组织中TLR-4/NF-κB和AMPK/Nrf2通路蛋白表达情况;油红O染色观察肝脏组织病理学变化。结果表明,GPS可降低NAFLD大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、丙二醛(MDA)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、空腹血糖(FBG)和空腹胰岛素(FINS)的活性或含量,增强血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和高密度脂蛋白(HDL-C)含量,改善胰岛素抵抗情况,降低肝脏中白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、NF-κBp-p65和TLR-4的表达水平,提高p-AMPK与Nrf2蛋白表达水平。由此可见,GPS改善NAFLD的作用机制可能与抑制氧化应激、炎症反应和调控TLR-4/NF-κB、AMPK/Nrf2信号通路有关。
To explore the protective effect of gentiopicroside(GPS)on non-alcoholic fatty liver(NAFLD)rats and the effects of TLR-4/NF-κB and AMPK/Nrf2 pathways.Sixty SD rats were randomly divided into normal group,model group,metformin group(200 mg/kg)and GPS high,medium and low dose groups(120,60,30 mg/kg).The normal group was fed standard diet and the other groups were fed high-fat diet for 14 weeks to establish NAFLD model.Biochemical methods were used to detect the levels of liver function,oxidative stress and lipid accumulation.Enzyme-linked immunosorbent assay(ELISA)was used to detect insulin resistance and inflammatory factor levels.Western blot was used to detect the expression of TLR-4/NF-κB and AMPK/Nrf2 pathway proteins.Oil red O staining was used to observe the pathological changes of liver tissue.The results shows GPS reduces the activity or content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malondialdehyde(MDA),cholesterol(TC),triglyceride(TG),total low density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),fasting insulin(FINS)and insulin resistance index(HOMA-IR),enhances the activity of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and high density lipoprotein cholesterol(HDL-C),reduces the levels of interleukin-1β(IL-1β),interleukin-6(IL-6),Tumor necrosis factor-α(TNF-α),NF-κBp-p65 and TLR-4 in the liver,increase the expression levels of p-AMPK and Nrf2.In conclusion,the mechanism of GPS to improve NAFLD may be related to inhibition of oxidative stress,inflammatory and regulation of TLR-4/NF-κB and AMPK/Nrf2 signaling pathways.