烟酸对C57BL/6J小鼠脂肪组织、血脂和主动脉粥样硬化的影响

Effects of Niacin on C57BL/6J mice’adipose tissue, serum lipid and atherosclerosis

目的以C57BL/6J小鼠为载体,以烟酸为干预药物,探索脂肪组织、血脂和主动脉粥样硬化三者间的潜在关系。方法将28只雄性C57BL/6J小鼠随机分为对照组(n=8)、模型组(n=10)和烟酸干预组(n=10),分别给予普通饲料、高胆固醇饲料、高胆固醇饲料+1%烟酸(w/w)处理。14周后酶法和免疫比浊法检测血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和载脂蛋白A-(IapoA-I)的含量;HE染色观察主动脉病理形态学改变;高效液相色谱法检测主动脉壁和腹股沟皮下脂肪组织胆固醇含量;RT-PCR检测腹股沟皮下脂肪组织LXRα、ABCA1和ABCG1mRNA的表达。结果对照组、模型组和烟酸干预组脂肪组织胆固醇含量分别为(3.13±0.19)、(20.81±1.97)和(4.00±0.81)mg/g;相对于模型组,烟酸干预可分别上调脂肪组织胆固醇外流调控子LXRα、ABCA1和ABCG1mRNA144%、47.3%和73.8%,降低血清TG、TC和LDL-C而升高HDL-C和apoA-I;Pearson相关分析显示动脉壁胆固醇含量与内膜厚度/中膜厚度比值正相关(r=0.58,P<0.05);烟酸干预组血管壁良性重塑,内膜变薄、内膜厚度/中膜厚度比值降低,内皮下间隙脂质沉积尤其是胆固醇蓄积减少。结论烟酸干预促进了外周脂肪组织的胆固醇逆向转运,使得血液中脂质谱发生变化,进而影响了动脉壁内皮下间隙脂质尤其是胆固醇的蓄积,使血管壁发生良性重塑、动脉粥样硬化斑块消退。

【Objective】To investigate the effects of Niacin on C57BL/6J mice＇ adipose tissue,serum lipid and atherosclerosis,and furthermore to explore the potential relation among them.【Methods】Total 28 male C57BL/6J mice were randomly divided into 3 groups： control group （n =8）,model group （n =10）,Niacin treatment group （n = 10）,respectively fed with normal diet,high cholesterol diet,high cholesterol diet ＋1%（w/w） Niacin.After 14 weeks,serum lipid level （total triglyeride,total cholesterol,HDL cholesterol,LDL cholesterol and apoA-I） was measured by enzymatic method and by immunoturbidimetery.Lesions of aortic arteries were stained with hematoxylin eosin.The content of cholesterol in arterial wall and subcutaneous adipose tissue in groin was quantitated by high performance liquid chromatography.The expression of LXRα,ABCA1 and ABCG1 mRNA in subcutaneous adipose tissue was determined by RT-PCR.【Results】The content of cholesterol in subcutaneous adipose tissue in control group,model group,Niacin treatment group was （3.13 ± 0.19）,（20.81 ± 1.97） and （4.00 ± 0.81） mg/g,respectively.Compared with model group,Niacin treatment could increase the expression of LXRα,ABCA1 and ABCG1 mRNA 144% ,47.3% and 73.8% respectively.And furthermore,it could also downregulate the level of serum total triglyeride,total cholesterol and LDL cholesterol,upregulate the level of serum HDL cholesterol,apoA-I.Pearson correlation analysis showed that there was a positive relation between the content of cholesterol in arterial wall and the ratio of intima/media thickness （r =0.58,P 0.05）.In addition to those above,Niacin treatment could thin the intima thickness,decrease the ratio of intima/media thickness and downregulate the subendothelium lipid-accumulation,especially cholesterol -accumulation.【Conclusion】 Niacin treatment may promote the reverse cholesterol transport of peri-adipose tissue,bring the changes of serum lipid profile,and furthermore influence the subendothelium lipid -accumulation,especially cholesterol -accumulation,and subsequently reverse the aortic atherosclerosis.