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.
作者
许琼梅
高雅
李梓萌
韦日明
马晓辉
晋玲
张可锋
XU Qiong-mei;GAO Ya;LI Zi-meng;WEI Ri-ming;MA Xiao-hui;JIN Ling;ZHANG Ke-feng(College of Pharmacy,Guilin Medical University,Guilin 541004,China;College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China)
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2020年第10期1652-1658,共7页
Natural Product Research and Development
基金
国家自然科学基金(81860673)
广西八桂学者专项(2017143)。
