mfat-1小鼠胆固醇代谢特点及相关机制

The Characteristics of Cholesterol Metabolism and its Mechanism in mfat-1 Mice

目的探讨mfat-1小鼠高脂饮食后血清胆固醇水平、胆固醇合成与吸收效率的改变及相关机制。方法mfat-1小鼠及C57BL/6小鼠各12只分别作为实验组和对照组,高脂饲料喂养4周后,心脏取血并取肝脏组织,气相色谱法检测小鼠肝脏膜脂质内二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、二十二碳五烯酸(DPA)、α-亚麻酸(ALA)、亚油酸(LA)、花生四烯酸(AA)的含量及血浆中总胆固醇、胆固醇合成标志物(角鲨烯、2,4-脱氢胆甾烷醇)及吸收标志物(菜油固醇、β-谷固醇、豆固醇)水平的变化,ELISA法检测两组小鼠肝脏中胆固醇合成限速酶3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-COAR)的表达水平。结果实验组小鼠肝脏膜脂质内ω-6/ω-3多不饱和脂肪酸(PUFA)比例显著低于对照组(1.70比6.04,P<0.01),血浆中胆固醇合成标志物角鲨烯、2,4-脱氢胆甾烷醇水平明显低于对照组(分别为0.63±0.17比1.24±0.36,3.89±0.54比6.57±1.06,P<0.05),胆固醇合成限速酶HMG-COAR的表达较对照组显著降低(379.76±22.37比443.98±27.99,P<0.01);胆固醇吸收标志物菜油固醇、β-谷固醇和豆固醇水平也显著低于对照组(分别为16.10±2.28比21.24±2.96、1.07±0.18比1.76±0.43、28.78±5.60比42.30±5.81,P<0.01);总胆固醇水平较对照组降低(0.91±0.07比1.16±0.85,P<0.01)。结论mfat-1小鼠通过抑制胆固醇的合成及吸收两种途径降低体内总胆固醇水平。

Aim To observe the change of serum total cholesterol（ TC） and efficiency of the synthesis and absorption of cholesterol in the mfat-1 mice after high fat diet,and to explore the relative mechanism. Methods 12mfat-1 mice as experimental group and 12 C57BL / 6 mice as control group were given high fat diet for 4 weeks. Blood was taken from the heart,and the liver tissue extracted four weeks later. The content of liver lipids eicosapentaenoic acid（ EPA）,docosahexenoic acid（ DHA）,docosapentaenoic acid（ DPA）,α-linolenic acid（ ALA）,linoleic acid（ LA）,arachidonic acid（ AA）,serum TC,and the level of cholesterol synthesis markers（ squalene,desmosterol）,absorption markers（ campesterol,β-sitosterol,stigmasterol）,were determined with gas chromatogram. The express of cholesterol synthesis rate-limiting enzyme in liver,3-Hydroxy-3-methylglutaryl- coenzyme A reductase（ HMG-COAR）,were determined with ELISA. Results In the contents of liver membrance lipid,the ratio of ω-6 /ω-3 polyunsaturated fatty acids in the experimental group was significantly lower than that in the control group（ 1. 70 vs 6. 04,P 0. 01）. The levels of liver HMG-COAR in the experimental group were significantly lower than those in the control group（ 379. 76 ± 22. 37 vs 443. 98± 27. 99,P 0. 01）. The levels of plasma TC,cholesterol synthesis markers（ squalene,desmosterol） and absorption markers（ campesterol,β-sitosterol,stigmasterol） in the experimental group were significantly lower than those in the control group（ 0. 91 ± 0. 07 vs 1. 16 ± 0. 85,P 0. 01; 0. 63 ± 0. 17 vs 1. 24 ± 0. 36,3. 89 ± 0. 54 vs 6. 57 ± 1. 06,P 0. 05;16. 10 ± 2. 28 vs 21. 24 ± 2. 96,1. 07 ± 0. 18 vs 1. 76 ± 0. 43,28. 78 ± 5. 60 vs 42. 30 ± 5. 81,P 0. 01,respectively）.Conclusion The mfat-1 mice can inhibit cholesterol synthesis and absorption,thus decrease the total cholesterol.