激动β_3肾上腺素受体对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块的影响

Effect of β_3 adrenergic receptor on atherosclerotic plaques in apoE knockout mice

目的探讨激动β3肾上腺素受体(β3-AR)对载脂蛋白E基因敲除(apoE-/-)小鼠血脂、动脉粥样硬化(AS)斑块、B族Ⅰ型清道夫受体(SR-BⅠ)的影响。方法选择10周龄C57BL/6小鼠10只作为正常对照组(A组,等量生理盐水腹腔注射),10周龄apoE-/-小鼠50只,高脂饮食至36周龄时随机分为高脂模型组(B组,等量生理盐水腹腔注射)、阿托伐他汀阳性药物对照组(C组,10mg/kg灌胃)、β3-AR激动剂小剂量组(D组,1.65μg/kg腹腔注射)、β3-AR激动剂大剂量组(E组,3.0μg/kg腹腔注射)与β3-AR拮抗剂组(F组,5.0μg/kg腹腔注射),分别给予β3-AR激动剂或β3-AR拮抗剂腹腔注射2次/周,共12周。48周龄时全自动生化仪检测小鼠血脂,取胸主动脉行病理观察,Western blot测定SR-BⅠ蛋白表达水平的变化。结果与B组比较,C组、D组、E组TC、VLDL/LDL-C显著下降(P<0.01);胸主动脉粥样斑块面积减小(P<0.01);SR-BⅠ蛋白表达水平显著上调(P<0.05)。D组、E组TG水平显著下降(P<0.01)。结论激动β3-AR通过改善apoE-/-高脂小鼠血脂代谢,上调SR-BⅠ,促进胆固醇逆转运,进而起到了减小胸主动脉斑块面积、抗AS的作用。

Objective To study the effect of β3 adrengerdic receptor （β3-AR） on blood lipid,atherosclerotic plaques, scavenger receptor B class type I （SR-B1） in apoE-/- knockout mice. Methods Ten C57BL/6 mice aged 10 weeks served as a nomal control group （group A）. Fifty apoE/ knockout mice aged 10 weeks fed with high fat food to 36 weeks old were randomly divided into high-fat model group （group B）,intragastric atorvatin （10 mg/kg） treatment group （group C）, small β3- AR dose （1.65μg/kg） agonist treatment group （group D） ,large β3-AR dose （3.0μg/kg） agonist treatment group （group E） and β3-AR antagonist treatment group （group F） and received intra abdominal injection of β3-AR agonist and antagonist,respectively, twice a week for 12 weeks. The serum blood lipid levels were measured with automatic biochemical analyzer, the lesions of thorac- ic aorta were observed, and the expression of SR-B I was detected by Western blot in 48 weeks old mice. Results The serum TC and VLDL/LDL-C levels were significantly lower, the area of thoracic aorta plaques was significantly smaller, and the expression level of SR-B I was significantly higher in groups C,D and E than in group B （P〈0.01）. The serum level of TG was signifi- cantly lower in groups D and E than in groups B and C （P〈0.01）. Conclusion Excited β3-AR reverses cholesterol and reduces area of thoracic aorta plaques by improving blood lipid metabolism and upregulating expression of SR-B I , thus playing a role in preventing atherosclerois.