高强度间歇运动对自发性高血压大鼠G蛋白耦联受体激酶2的影响

Effects of high-intensity interval training on G protein-coupled receptor kinase-2 levels in the hearts and ad-renal glands of spontaneously hypertensive rats

目的观察高强度间歇运动(HIIT)对自发性高血压大鼠(SHR)心脏及肾上腺G蛋白耦联受体激酶2(GRK2)表达的影响,探讨HIIT干预改善高血压交感神经过度兴奋的可能机制。方法采用随机数字表法将20只雄性SHR大鼠分为安静对照组及HIIT组,同时选取10只鼠龄与之匹配的Wistar-Kyoto雄性大鼠纳入正常血压组。正常血压组及安静对照组大鼠均置于鼠笼内安静饲养8周,HIIT组则给予8周HIIT干预。待实验进行8周后,采用无创血压仪测定大鼠尾动脉血压,采用超声心动图检测心脏结构及功能,通过采集心电信号对大鼠心率变异性(HRV)进行频域分析;采用高压液相色谱法测定大鼠血浆肾上腺素及去甲肾上腺素浓度;采用Western blot法检测大鼠心肌GRK2、β1-肾上腺素受体(β1-AR)及肾上腺GRK2、α2-肾上腺素受体(α2-AR)蛋白表达情况。结果与正常血压组比较,安静对照组大鼠血压升高、心脏肥大、心功能降低,HRV表现为交感神经过度兴奋,血浆肾上腺素及去甲肾上腺素浓度升高,心脏及肾上腺GRK2表达均上调,心脏β1-AR及肾上腺α2-AR表达均下调(P<0.05);与安静对照组比较,HIIT组虽然心脏肥大并未改善,但血压明显下降,心功能提高,交感神经过度兴奋得到抑制,血浆肾上腺素及去甲肾上腺素浓度下降,心脏及肾上腺GRK2表达均下调,心脏β1-AR及肾上腺α2-AR表达均上调(P<0.05)。结论HIIT干预能显著改善SHR大鼠交感神经过度兴奋状态并提高心功能,其治疗机制可能与下调心脏及肾上腺GRK2表达有关。

Objective To observe the effect of high-intensity interval training(HIIT)on G protein-coupled receptor kinase-2(GRK2)levels in the hearts and adrenal glands of spontaneously hypertensive rats(SHRs)and explore how exercise might improve sympathetic over-excitation.Methods Twenty male SHRs were divided randomly into a sedentary control group and an HIIT group.Ten age-matched,male Wistar-Kyoto rats without hypertension served as the control group.The rats of the control and sedentary control groups were housed in cages at rest while those of the HIIT group underwent eight weeks of HIIT.Caudal artery pressure,cardiac structure and function,and heart rate variability(HRV)were determined using a non-invasive blood pressure tester,echocardiograms,and electrocardiograms.The plasma concentrations of epinephrine and norepinephrine,and the expression of GRK2 andβ1-adrenoceptor(β1-AR)protein were measured in the rats′hearts,and GRK2 andα2-adrenoceptor(α2-AR)protein were measured in their adrenal glands using high-pressure liquid chromatography and western blotting.Results Compared with the normotensive control group,animals in the sedentary control group showed elevated blood pressure,cardiac hypertrophy,reduced heart function,sympathetic over-excitation manifested by HRV,increased plasma epinephrine and norepinephrine concentrations,up-regulated GRK2 protein expression in the heart and adrenal gland,but down-regulatedβ1-AR in the heart and down-regulatedα2-AR in the adrenal gland.Compared with the sedentary control group,the HIIT group did not show improved cardiac hypertrophy,but it did show reduced blood pressure,enhanced heart function,suppressed sympathetic over-excitation,as well as lowered plasma epinephrine and norepinephrine concentrations,on average.The expression of GRK2 in the heart and adrenal gland was significantly down-regulated,while that ofβ1-AR in the heart and ofα2-AR in the adrenal gland were significantly up-regulated,on average.Conclusions HIIT can alleviate sympathetic over-excitation and enhance heart function despite spontaneous hypertension,at least in rats.The therapeutic mechanism may be related with the down-regulation of GRK2 expression in the heart and adrenal gland.