中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
6期
472-479
,共8页
动脉粥样硬化%生育三烯酚%糖代谢%过氧化物酶体增殖物激活受体
動脈粥樣硬化%生育三烯酚%糖代謝%過氧化物酶體增殖物激活受體
동맥죽양경화%생육삼희분%당대사%과양화물매체증식물격활수체
atherosclerosis%tocotrienol%glucose metabolism%peroxisome proliferator-activated receptor
目的 探讨富含生育三烯酚的棕榈油(TRF)对动脉粥样硬化小鼠糖代谢的影响及其可能的作用机制.方法 载脂蛋白E基因缺陷(ApoE~(-/-))小鼠分为模型对照组、TRF 0.05%和0.2%(W/W) 组.TRF均匀混于饲料中,各组饲料中添加10%(W/W) 的脂肪和0.2%(W/W)的胆固醇诱导动脉粥样硬化的形成.小鼠经TRF处理12和14周后分别进行口服葡萄糖耐量实验 (OGTT) 和胰岛素耐量实验 (ITT);用相应试剂盒检测血清中总胆固醇 (TC)、甘油三酯 (TG)、游离脂肪酸 (FFA) 和胰岛素的含量;实时荧光定量PCR分析白色脂肪组织 (WAT) 中过氧化物酶体增殖物激活受体γ(PPARγ)、脂联素和葡萄糖转运体4(Glut4)的mRNA水平;利用荧光素酶报告系统检测TRF对PPRAγ的激活作用.结果 OGTT和ITT实验显示,在非禁食和禁食的情况下,TRF均能够降低ApoE~(-/-)小鼠的血糖,改善胰岛素的敏感性;TRF组小鼠血清中TG和FFA的水平均低于模型对照组;在WAT中,与模型对照组相比,TRF 0.2%组上调脂联素mRNA水平(1.73±0.32)倍,TRF 0.05%和0.2%组分别增加Glut4 mRNA水平(1.89±0.24)和(2.01±0.61)倍,PPARγ mRNA水平没有改变.荧光素酶报告系统检测结果显示,TRF对PPARγ-配体结合结构域、PPARγ1和PPARγ2的激活作用分别是溶剂对照组的(2.7±0.2), (6.1±0.6)和(5.3±0.1)倍.结论 TRF能够很好地改善动脉粥样硬化小鼠的糖代谢, TRF发挥这些作用的部分原因是通过激活PPARγ来实现的.
目的 探討富含生育三烯酚的棕櫚油(TRF)對動脈粥樣硬化小鼠糖代謝的影響及其可能的作用機製.方法 載脂蛋白E基因缺陷(ApoE~(-/-))小鼠分為模型對照組、TRF 0.05%和0.2%(W/W) 組.TRF均勻混于飼料中,各組飼料中添加10%(W/W) 的脂肪和0.2%(W/W)的膽固醇誘導動脈粥樣硬化的形成.小鼠經TRF處理12和14週後分彆進行口服葡萄糖耐量實驗 (OGTT) 和胰島素耐量實驗 (ITT);用相應試劑盒檢測血清中總膽固醇 (TC)、甘油三酯 (TG)、遊離脂肪痠 (FFA) 和胰島素的含量;實時熒光定量PCR分析白色脂肪組織 (WAT) 中過氧化物酶體增殖物激活受體γ(PPARγ)、脂聯素和葡萄糖轉運體4(Glut4)的mRNA水平;利用熒光素酶報告繫統檢測TRF對PPRAγ的激活作用.結果 OGTT和ITT實驗顯示,在非禁食和禁食的情況下,TRF均能夠降低ApoE~(-/-)小鼠的血糖,改善胰島素的敏感性;TRF組小鼠血清中TG和FFA的水平均低于模型對照組;在WAT中,與模型對照組相比,TRF 0.2%組上調脂聯素mRNA水平(1.73±0.32)倍,TRF 0.05%和0.2%組分彆增加Glut4 mRNA水平(1.89±0.24)和(2.01±0.61)倍,PPARγ mRNA水平沒有改變.熒光素酶報告繫統檢測結果顯示,TRF對PPARγ-配體結閤結構域、PPARγ1和PPARγ2的激活作用分彆是溶劑對照組的(2.7±0.2), (6.1±0.6)和(5.3±0.1)倍.結論 TRF能夠很好地改善動脈粥樣硬化小鼠的糖代謝, TRF髮揮這些作用的部分原因是通過激活PPARγ來實現的.
목적 탐토부함생육삼희분적종려유(TRF)대동맥죽양경화소서당대사적영향급기가능적작용궤제.방법 재지단백E기인결함(ApoE~(-/-))소서분위모형대조조、TRF 0.05%화0.2%(W/W) 조.TRF균균혼우사료중,각조사료중첨가10%(W/W) 적지방화0.2%(W/W)적담고순유도동맥죽양경화적형성.소서경TRF처리12화14주후분별진행구복포도당내량실험 (OGTT) 화이도소내량실험 (ITT);용상응시제합검측혈청중총담고순 (TC)、감유삼지 (TG)、유리지방산 (FFA) 화이도소적함량;실시형광정량PCR분석백색지방조직 (WAT) 중과양화물매체증식물격활수체γ(PPARγ)、지련소화포도당전운체4(Glut4)적mRNA수평;이용형광소매보고계통검측TRF대PPRAγ적격활작용.결과 OGTT화ITT실험현시,재비금식화금식적정황하,TRF균능구강저ApoE~(-/-)소서적혈당,개선이도소적민감성;TRF조소서혈청중TG화FFA적수평균저우모형대조조;재WAT중,여모형대조조상비,TRF 0.2%조상조지련소mRNA수평(1.73±0.32)배,TRF 0.05%화0.2%조분별증가Glut4 mRNA수평(1.89±0.24)화(2.01±0.61)배,PPARγ mRNA수평몰유개변.형광소매보고계통검측결과현시,TRF대PPARγ-배체결합결구역、PPARγ1화PPARγ2적격활작용분별시용제대조조적(2.7±0.2), (6.1±0.6)화(5.3±0.1)배.결론 TRF능구흔호지개선동맥죽양경화소서적당대사, TRF발휘저사작용적부분원인시통과격활PPARγ래실현적.
AIM To investigate the effect of tocotrienol rich fraction of palm oil (TRF) on glucose metabolism in atherosclerotic mice and the possible mechanism. METHODS Apolipoprotein E gene deficient(ApoE~(-/-)) mice were divided into 3 groups as model control, TRF 0.05% and 0.2%(W/W) groups. 10% (W/W) fat and 0.2% (W/W) cholesterol were added into the diets to induce atherosclerosis formation. Oral glucose tolerance test and insulin tolerance test were conducted after mice were treated by TRF for 12 and 14 weeks respectively. Serum cholesterol, triglyceride, free fatty acid, and insulin levels were measured using corresponding kits. The mRNA expression levels for peroxisome proliferator-activated receptor γ(PPARγ), adiponectin and glucose transporter 4 (Glut4) in white adipose tissue (WAT) were determined by using quantitative real-time PCR. Activation of PPARγ by TRF was tested using luciferase reporter assays. RESULTS Compared with the model control group, TRF decreased non-fasting or fasting blood glucose levels and improved insulin sensitivity of ApoE~(-/-) mice. Both TRF groups showed decreased levels of triglyceride and free fatty acid. The mRNA level of adiponectin in WAT was up-regulated by (1.73±0.32) times in TRF 0.2% group compared with the control group. Glut4 mRNA level was increased (1.89±0.24) and (2.01±0.61) times compared with control group in TRF 0.05% group and TRF 0.2% group respectively. The fold inductions of TRF on PPARγ-ligand-binding domain, PPARγ1 and PPARγ2 activities were (2.7±0.2), (6.1±0.65) and (5.3±0.1) times compared with DMSO by using luciferase reporter assay. CONCLUSION TRF can improve glucose metabolism in atherosclerotic mice and this effect may be partly due to modulating the activity of PPARγ.
