nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2023, 02, v.46 103-106
科罗索酸对高脂饲料诱导小鼠非酒精性脂肪肝的保护作用及其机制
基金项目(Foundation): 吉林省大学生创新创业训练计划项目(编号:S202210184037); 国家自然科学基金项目(81660614;82060674)
邮箱(Email): gcpiao@ybu.edu.cn;hdyuan@ybu.edu.cn.;
DOI: 10.16068/j.1000-1824.2023.02.004
摘要:

[目的]探讨科罗索酸(CA)对高脂饲料(HFD)诱导小鼠非酒精性脂肪肝的保护作用及其机制.[方法]选择5周龄C57BL/6j雄性小鼠随机分为5个组,即正常(CON)组、模型(HFD)组、CA低剂量(10 mg/kg CA,CAL)组、CA高剂量(20 mg/kg CA,CAH)组及阳性对照(300 mg/kg二甲双胍,MET)组.CON组给予10 kcal%正常饲料喂养,其余4个组均给予60 kcal%HFD喂养,共喂养13周,最后4周分别灌胃给予各组小鼠相应剂量的药物,每日1次.[结果]与HFD组比较,CAH组小鼠三酰甘油和总胆固醇水平均显著降低(P<0.001),肝脏组织脂滴蓄积明显减少(P<0.001). CA呈剂量依赖性地激活小鼠肝脏组织中AMPK和ACC蛋白质的表达(P<0.001),抑制SREBP1c、FAS及SCD1等基因表达(P<0.001),并升高PPARα和CD36基因表达(P<0.001).[结论]C A可能通过激活AMPK信号通路来调控肝脏脂质积蓄.

Abstract:

OBJECTIVE To investigate the protective effect of corosolic acid(CA) on mice nonalchoholic fatty liver disease induced by high fat diet(HFD)and its mechanism. METHODS C57BL/6j male mice aged 5 weeks were randomly divided into 5 groups, control group(CON),model group(HFD), CA low dose group(10 mg/kg CA, CAL),CA high dose group(20 mg/kg CA, CAH) and positive control group(300 mg/kg metformin, MET). The CON group was fed with 10 kcal% normal diet, and the other 4 groups were fed with 60 kcal% HFD for 13 weeks. In the last 4 weeks, the mice in each group were given the corresponding dose of medication by gavage once a day. RESULTS Compared with the HFD group, the levels of triglyceride and total cholesterol in CAH group were significantly reduced(P<0.001), and the accumulation of lipid droplets in liver tissue was significantly reduced(P<0.001). CA activated the expressions of AMPK and ACC protein in mice liver in a dose-dependent manner(P<0.001), inhibited the expressions of SREBP1c, FAS, SCD1 and other genes(P<0.001), and increased the expressions of PPARα and CD36 genes(P<0.001). CONCLUSION CA might regulate lipid accumulation in the liver by activating AMPK signaling pathway.

参考文献

[1]郭朝阳,芮法娟,李婕.非酒精性脂肪肝炎新药研发的一些关键因素[J].临床肝胆病杂志,2021,37(6):1254-1258.

[2]张夏,罗伟生,胡振斌,等.非酒精性脂肪肝中医药研究进展[J].辽宁中医药大学学报,2018,20(7):180-182.

[3]YOUNOSSI Z M,KOENIG A B,ABDELATIF D,et al..Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J].Hepatology,2016,64(1):73-84.

[4]张建秀,柳慧哲,朴光春,等.科罗索酸药理作用研究进展[J].国际药学研究杂志,2019,46(1):22-26.

[5]KU C Y,WANG Y R,LIN H Y,et al..Corosolic acid inhibits hepatocellular carcinoma cell migration by targeting the VEGFR2/Src/FAK pathway[J].PLo SOne,2015,10(5):e0126725.

[6]SHI L,ZHANG W,ZHOU Y Y,et al..Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation[J].Eur J Pharmacol,2008,584(1):21-29.

[7]ZONG W,ZHAO G Y.Corosolic acid isolation from the leaves of eriobotrta japonica showing the effects on carbohydrate metabolism and differentiation of3T3-L1 adipocytes[J].Asia Pac J Clin Nutr,2007,16(S1):346-352.

[8]BALAKRISHNAN A,AL ASSAF A H.Corosolic acid suppresses the expression of inflammatory marker genes in CCL4-induced-hepatotoxic rats[J].Pak JPharm Sci,2016,29(4):1133-1138.

[9]KAWANO Y,COHEN D E.Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease[J].J Gastroenterol,2013,48(4):434-441.

[10]SHENG D,ZHAO S,GAO L,et al..Babao Dan attenuates high-fat diet-induced non-alcoholic fatty liver disease via activation of AMPK signaling[J].Cell Biosci,2019,9:77.

[11]郝梦娇,党院霞,周欣欣,等.黄芪散对高脂血症大鼠AMPK/ACC/CPT1通路的影响[J].中国中药杂志,2018,43(12):2586-2592.

[12]FANG K,WU F,CHEN G,et al..Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells[J].BMC Complement Altern Med,2019,19(1):255.

[13]LI X,LI Y,YANG W,et al..SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes[J].J Steroid Biochem Mol Biol,2014,143:174-182.

[14]LI Y,XU S,MIHAYLOVA M M,et al..AMPKphosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice[J].Cell Metab,2011,13(4):376-388.

[15]RUDERMAN N B,CARLING D,PRENTKI M,et al..AMPK,insulin resistance,and the metabolic syndrome[J].J Clin Invest,2013,123(7):2764-2772.

[16]CAO S,LI B,YI X,et al..Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes[J].PLo S One,2012,7(12):e51709.

基本信息:

DOI:10.16068/j.1000-1824.2023.02.004

中图分类号:R285.5

引用信息:

[1]王喆,王宇琪,张彩云,等.科罗索酸对高脂饲料诱导小鼠非酒精性脂肪肝的保护作用及其机制[J].延边大学医学学报,2023,46(02):103-106.DOI:10.16068/j.1000-1824.2023.02.004.

基金信息:

吉林省大学生创新创业训练计划项目(编号:S202210184037); 国家自然科学基金项目(81660614;82060674)

投稿时间:

2023-05-05

投稿日期(年):

2023

终审时间:

2023-06-06

终审日期(年):

2023

审稿周期(年):

1

发布时间:

2023-06-26

出版时间:

2023-06-26

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文