激动β_3肾上腺素受体对载脂蛋白E基因敲除小鼠肺脏血管紧张素受体表达的影响

Effect of β_3-AR activation on expression of angiotensin receptors in lungs of 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-/-)老年高脂小鼠肺脏血管紧张素受体(ATR)表达的影响。方法野生型C57BL/6J小鼠10只作为对照组,apoE-/-老年高脂小鼠40只随机分为高脂模型组、β3-AR激动剂小剂量组(小剂量组)、β3-AR激动剂大剂量组(大剂量组)和β3-AR拮抗剂组(拮抗剂组),每组10只。给予高脂饮食饲养至36周龄后分别给予药物干预12周。采用全自动生化分析仪检测TC和VLDL/LDL-C水平,实时定量PCR或Western blot测定肺组织β3-AR、AT1R和AT2R的mRNA及蛋白表达水平。结果与高脂模型组比较,小剂量组、大剂量组TC和VLDL/LDL-C水平明显降低[(18.27±1.30)mmol/L,(17.06±1.50)mmol/L vs(22.20±1.29)mmol/L和(14.31±0.31)mmol/L,(12.78±0.55)mmol/L vs(19.41±0.40)mmol/L,P<0.01]。与对照组比较,高脂模型组和拮抗剂组AT1R mRNA和AT1R蛋白水平明显升高,AT2R mRNA、β3-AR蛋白水平明显降低(P<0.05)。与高脂模型组比较,小剂量组和大剂量组AT1R表达下调,AT2R和β3-AR表达上调(P<0.05,P<0.01)。结论β3-AR激动剂在改善apoE-/-老年高脂小鼠血脂代谢紊乱的同时,影响了肺组织β3-AR和ATR各亚型表达,这种受体间交互作用可能与维持高脂血症条件下肺脏的正常功能有关。

Objective To study the effect ofβ3-AR activation on expression of angiotensin receptors in lungs of aged apoE/knockout mice.Methods Ten C57BL/6Jmice served as a control group,and 40apoE/knockout mice were randomly divided into hyperlipidemia model group,lowβ3-AR agonist group（low dose group）,highβ3-AR agonist group（high dose group）andβ3-AR antagonist group（antagonist group）.The animals underwent drug treatment for 12 weeks.Their serum TC and VLDL/LDL-C levels were measured by biochemical analyzer.Theβ3-AR,AT1 R and AT2 R mRNA and protein expressions in lung were detected by RT-PCR or Western blot.Results The AT1 R mRNA and protein expression levels were higher while the AT2 R mRNA andβ3-AR protein expression levels were significantly lower in model and antagonist groups than in control group（P〈0.05）.Compared with model group,the AT1 R expression were down-regulated and AT2 R andβ3-AR were up-regulated in the low dose and high dose groups.Conclusion β3-AR activation improves lipid metabolism disorder and affects expression levels ofβ3-AR and ATR subtypes in lungs of aged apoE/knockout mice,indicating that the sympathetic adrenergic system interacts with the angiotensin system in the lungs of aged apoE/knockout mice.These interaction may be associated with the maintenance of normal lung function in hyperlipidemia.