应用骨髓移植研究巨噬细胞脂蛋白脂酶对严重高甘油三酯血症小鼠脂代谢的作用

The Effect of Bone Marrow Derived Lipoprotein Lipase on Lipid Metabolism in Severe Lipoprotein Lipase Deficient Hypertriglyceridemic Mice

目的研究骨髓中巨噬细胞来源的脂蛋白脂酶(LPL)对遗传性极高甘油三酯血症小鼠血浆脂蛋白代谢的作用。方法将8只雌性脂蛋白脂酶基因缺陷(LPL-/-,LK)小鼠随机分为两组,用1 000 rad137Cs照射,6 h后分别尾静脉注射脂蛋白脂酶基因缺陷的雄性小鼠及野生型(WT)雄性小鼠的骨髓。骨髓移植后通过眶静脉采血收集小鼠血浆,监测血浆甘油三酯、胆固醇、血浆脂蛋白脂酶活性等指标的变化,并用快效液相色谱技术检测血浆脂蛋白的分布。结果移植后第4周,与LPL-/-→LPL-/-骨髓移植组相比,WT→LPL-/-骨髓移植组小鼠血浆甘油三酯水平降低83.2%(P<0.05,n=4),胆固醇水平降低74.4%(P<0.05,n=4)。与骨髓移植前相比,WT→LPL-/-骨髓移植组小鼠血浆甘油三酯水平降低86.2%(P<0.05,n=4),胆固醇水平降低78.8%(P<0.01,n=4),脂蛋白脂酶活性增加4.5倍(P<0.05,n=4)。LPL-/-→LPL-/-骨髓移植组小鼠血浆甘油三酯、胆固醇水平以及血浆脂蛋白脂酶活性较移植前均无明显改变。结论骨髓巨噬细胞来源的脂蛋白脂酶对脂代谢具有重要的调节作用,可有效改善遗传性极高甘油三酯血症小鼠的高脂血症。

Aim To study the effects of macrophage-derived lipoprotein lipase（LPL） on the lipid metabolism in inherited hypertriglyceridemia mice. Methods After lethal irradiation,8 female LPL-deficient（LPL-/-,LK） mice were divided into two groups and reconstituted by bone marrow transplantation（BMT）from male C57BL（LPL＋/＋,WT） and LK mice,respectively.Plasma levels of triglyceride,total cholesterol were surveyed,plasma lipoprotein profile was detected by fast protein liquid chromatography（FPLC）,and LPL activities were assayed at week 4 post-BMT. Results It was demonstrated that plasma triglyceride（TG） and cholesterol（Chol） levels in BMT（WT→LPL-/-） mice were reduced by 83.2%（P〈0.05,n=4） and 74.4%（P〈0.05,n=4） compared with those in LPL-/-→LPL-/-mice,while similar reduction by 86.2% and 78.8% in TG and Chol before and after BMT were observed in WT→LPL-/-mice.Post-heparin plasma LPL activities were increased by 4.5-fold after BMT.There were no effects of BMT in LK→LK mice on TG,Chol and LPL activities. Conclusion Macrophage-derived LPL plays a significant role in the lipid metabolism,and improves lipoprotein disorder in inherited hypertriglyceridemia mice.