激动β_3肾上腺素受体对载脂蛋白E基因敲除小鼠肾脏血管紧张素受体各亚型表达水平影响的研究

Effect of Beta3-adrenoceptor activation on interaction of kidney angiotensin Ⅱ receptors in aging apo E^(-/-) mice

目的:探讨激动β3肾上腺素受体(β3-AR)对老年载脂蛋白E基因敲除(apo E-/-)小鼠血脂、血糖和肾脏血管紧张素受体(ATR)各亚型表达水平的影响。方法:选择10周龄,C57BL/6J小鼠10只,予正常饮食,作为正常对照组(A组),另选10周龄apo E-/-小鼠50只给予高脂饲料饲养,至36周龄时随机分为5组(每组10只),分别为高脂模型组(B组)、阿托伐他汀组(C组)、β3-AR激动剂小剂量组(D组)、β3-AR激动剂大剂量组(E组)和β3-AR拮抗剂组(F组),共干预12周。48周龄时,采用全自动生化仪检测各组小鼠血浆非高密度脂蛋白胆固醇(n HDL-C)、葡萄糖和胰岛素水平,采用实时定量PCR和Western blot检测各组小鼠肾脏组织AT1R与AT2R的mRNA与蛋白的表达水平。结果:与A组相比,B组血浆n HDL-C、葡萄糖及胰岛素水平显著升高(P<0.01),肾脏组织AT1R与AT2R表达水平显著上调(P<0.01);与B组相比,D组和E组血浆n HDL-C、葡萄糖和胰岛素水平显著降低(P<0.01),肾脏组织AT1R表达水平显著下调(P<0.05),AT2R表达水平显著上调(P<0.05)。结论:长期激动β3-AR能够改善apo E-/-老年高脂小鼠糖、脂代谢紊乱,使肾脏组织高脂条件下AT1R与AT2R表达水平发生反向调节,表明β3-AR与ATR之间存在交互作用,这种受体间的交互作用可能对高脂血症导致的肾功能损伤起到有益的保护作用。

Objective： To study the effects of β3-adrenoceptOr activation on the interaction of kidney an- giotensin II receptor subtypes in aging apolipoprotein E knockout （apoE-/-） mice. Methods ：Ten wild-type C57BL/6J mice served as normal control group （group A） and 50 age matched apoE-/- mice were randomly di- vided into hyperlipidaemia model group, atorvastatin group, low-dose β3-adrenoceptor agonist group, high-dose β3-adrenoceptor agonist group and β3-adrenoceptor antagonist group. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Serum non-high density lipoprotein cholesterol, blood glucose and insulin levels in 48 week-old mice were measured using an automatic biochemical detector. Expression of angiotensin II type 1 and type 2 receptors in kidney tissues were detected by RT-PCR and Western blot, respectively. Results ：β3-adre- noceptor agonist could decrease non-high density lipoprotein cholesterol, glucose and insulin in aged apoE-/- mice （P 〈 0. 01 ） and down-regulated the expression of angiotensin II type 1 receptor （P 〈 0. 01 ）, and up-regu-lated angiotensin II type 2 receptor which were significantly increased in model mice （P 〈 0. 01 ）. Conclusion ： β3-adrenoceptor agonist improved lipid and glucose metabolism, and decreased the expression of up-regulated angiotensin II type 1 receptor, and increased the down-regulated angiotensin II type 2 receptor, indicating that there are interaction between β3-adrenoceptor and angiotensin II type receptors, which will protect the kidney function.