摘要
肝脏脂质沉积是肥胖症的一个表现,现今药物治疗是最重要的手段。安石榴苷(punicalagin,PU)是石榴皮中提取的一种多酚类物质,是一种潜在的抗肥胖物质。该研究将60只C57BL/6J小鼠随机分为正常组和模型组2组,以高脂饲料对模型组建立单纯肥胖模型12周后,将成功建立的肥胖模型再重新分组为模型组、奥利司他组、PU低剂量组、PU中剂量组、PU高剂量组。正常组持续喂养常规饲料,其他组喂养高脂饲料,并每周记录各组小鼠体质量和摄食情况;8周后,全自动生化仪测定各组小鼠血清中血脂四项的含量水平;检测口服葡萄糖耐量性和腹腔注射胰岛素敏感性;苏木素-伊红(hemoxylin-eosin,HE)染色观察各组小鼠肝脏及脂肪组织病理变化;实时定量PCR(Q-PCR)法和蛋白印迹方法检测肝脏中PPARγ、C/EBPα的mRNA表达及AMPK、ACC、CPT1A的mRNA和蛋白表达水平。最后模型组小鼠的体质量,Lee′s指数,血清甘油三酯(total glyceride,TG)、胆固醇(total cholesterol,TC)和低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)含量较正常组显著升高,高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)含量较正常组明显降低;肝脏内脂肪沉积显著增加;肝脏PPARγ、C/EBPαmRNA含量和ACC蛋白表达量明显增加,AMPK、CPT-1αmRNA表达量明显减少,AMPK和CPT1A蛋白表达量明显减少。经PU处理后,干预组小鼠上述指标显示明显反转。总之,PU可降低肥胖小鼠体质量,且较有效地抑制其摄食量,同时具有调节与肥胖相关的血脂和糖代谢异常的作用,能够显著改善肝脏脂肪沉积,从机制分析PU可能通过活化AMPK/ACC通路下调脂质合成,上调脂质分解,调控肥胖小鼠肝脏脂质的沉积。
Hepatic lipid deposition is one of the basic manifestations of obesity,and nowadays pharmacological treatment is the most important tool.Punicalagin(PU),a polyphenol derived from pomegranate peel,is a potential anti-obesity substance.In this study,60 C57BL/6J mice were randomly divided into a normal group and a model group.After establishing a model of simple obesity with a high-fat diet for 12 weeks,the successfully established rat models of obesity were then regrouped into a model group,an orlistat group,a PU low-dose group,a PU medium-dose group,and a PU high-dose group.The normal group was kept on routine diet and other groups continued to feed the high-fat diet.The body weight and food intake were measured and recorded weekly.After 8 weeks,the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument.Oral glucose tolerance and intraperitoneal insulin sensitivity were tested.Hemoxylin-eosin(HE)staining was applied to observe the hepatic and adipose tissues.The mRNA expression levels of peroxisome proliferators-activated receptorγ(PPARγ)and CCAAT/enhancer-binding proteinα(C/EBPα)were determined by real-time quantitative polymerase chain reaction(RT-qPCR),and the mRNA and protein expression levels of adenosine 5’-monophosphate-activated protein kinase(AMPK),anterior cingulate cortex(ACC),and carnitine palmitoyltransferase 1A(CPT1A)were determined by Western blot.Finally,the body mass,Lee’s index,serum total glyceride(TG),serum total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were significantly higher and high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the model group as compared with the normal group.The fat deposition in the liver was significantly increased.The mRNA expression levels of hepatic PPARγand C/EBPαand the protein expression level of ACC were increased,while the mRNA and protein expression levels of CPT1A and AMPK were decreased.After PU treatment,the above indexes of obese mice were reversed.In conclusion,PU can decrease the body weight of obese mice and control their food intake.It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism,which can significantly improve hepatic fat deposition.Mechanistically,PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.
作者
热娜·吉恩斯
常占瑛
牛若惠
高晓黎
RENA Jiensi;CHANG Zhan-ying;NIU Ruo-hui;GAO Xiao-li(School of Pharmacy,Xinjiang Medical University,Urumuqi 830011,China;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Urumuqi 830011,China;Korla Hospital of the Second Division of Xinjiang Production and Construction Corps,Korla 841000,China;Key Laboratory of Active Components of Xinjiang Natural Medicine and Drug Release Technology,Urumuqi 830011,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第7期1751-1759,共9页
China Journal of Chinese Materia Medica
基金
省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2022-13)。