虾青素对肝脂代谢与昼夜节律的调节作用  

Astaxanthin Regulates Liver Lipid Metabolism and Circadian Gene Expression

作　　者：左正宇 邵洋 刘杨 卜怡然 王华林 李娜 刘志国 ZUO Zhengyu;SHAO Yang;LIU Yang;BU Yiran;WANG Hualin;LI Na;LIU Zhiguo(School of Biology and Pharmaceutical Engineering,Wuhan Polytechnic University,Wuhan 430023,China)

机构地区：[1]武汉轻工大学生物与制药工程学院,湖北武汉430023

出　　处：《食品科学》2019年第3期165-172,共8页Food Science

基　　金：国家自然科学基金面上项目(31271855);国家自然科学基金青年科学基金项目(31000772)

摘　　要：研究虾青素对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的干预作用及与代谢相关的昼夜节律紊乱的缓解作用。采用高脂/高胆固醇饲喂建立NAFLD小鼠模型和添加虾青素的干预模型。动物实验选用SPF级C57BL/6小鼠,随机分成正常组、高脂模型组和高脂添加虾青素组。采用常规酶联免疫吸附测定法测定血清中甘油三酯、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)浓度及谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate transaminase,AST)活力等肝损伤指标,苏木精-伊红染色法观察肝组织形态学变化,荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,qPCR)检测与肝脂代谢、胆固醇代谢、昼夜节律相关的基因表达及昼夜节律变化。结果显示:与正常组相比,高脂模型组小鼠体质量、肝脏指数、肥胖指数均高度显著增加(P<0.001),虾青素干预后肝脏指数、肥胖指数均极显著降低(P<0.01)。高脂饲喂导致小鼠血脂水平升高(HDL-C除外),尤其是LDL-C浓度升高明显,而虾青素干预可以有效降低TC和LDL-C浓度,并升高HDL-C浓度,改善脂质的代谢。高脂/高胆固醇饲喂会高度显著升高小鼠血清ALT、AST活力(P<0.001),造成肝损伤。与高脂模型组相比,虾青素干预可极显著降低小鼠ALT、AST活力(P<0.01),缓解肝脏损伤,并明显改善肝脏脂质代谢关键酶的基因表达,包括脂肪酸合成酶和胆固醇合成关键酶羟甲基戊二酸单酰辅酶A还原酶。同时,虾青素干预也增加了胆固醇7α-羟化酶的表达量,促进胆固醇氧化。虾青素调节上述基因的表达具有昼夜节律性,能够缓解或修正由高脂导致的生物钟节律相关因子时钟昼夜节律调节器及脑和肌肉芳香烃受体核转运体样蛋白1以及肝脏脂质代谢关键基�In the current study,we aimed to investigate the protective effects of astaxanthin(AX)against non-alcoholic fatty liver disease(NAFLD)via a circadian rhythm-related mechanism.A high-fat and high-cholesterol diet was adopted to build an NAFLD mouse model.Male SPF C57BL/6 mice were divided into three groups:normal chow(control),HFD model,and HFD+AX groups.After 12 weeks of feeding,blood biochemical indexes such as triglyceride,total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),as well as liver injury indexes such as alanine aminotransferase(ALT)and aspartate transaminase(AST)were determined.Morphological variations of liver tissue were observed by hematoxylin-eosin staining.Real-time quantitative polymerase chain reaction(qPCR)was used to examine the expression levels of genes related to liver lipid metabolism,cholesterol metabolism and circadian rhythm.The results showed that body mass,liver/body mass ratio and obesity index of mice in the HFD group were significantly higher when compared with the control group(P﹤0.001).Both liver/body mass ratio and obesity index dropped dramatically after dietary supplementation of AX(P﹤0.01).High-fat fed mice showed higher blood lipid levels(except HDL-C);in particular,a significant increase was observed in LDL-C.Dietary supplementation of AX effectively reduced TC and LDL-C,increased HDL-C,and improved lipid metabolism when compared with the HFD group.HFD significantly increased the levels of serum ALT and AST and caused liver injury(P﹤0.001).These effects could be significantly rescued by AX(P﹤0.01).Moreover,AX could remarkably improve the expression of key enzyme genes related to liver lipid metabolism including fatty acid synthase and hydroxymethylglutaryl-CoA reductase.In addition,AX also increased the expression of cholesterol 7α-hydroxy-lase,promoted cholesterol oxidation in liver.AX regulated the expression of these genes in a circadian rhythm-dependent way.AX could alleviate or correct the disorders

关 键 词：虾青素 非酒精性脂肪性肝病 昼夜节律 

分 类 号：R151.2[医药卫生—营养与食品卫生学]