美托洛尔对老年男性非ST段抬高型心肌梗死病人淋巴细胞GRK2表达水平的影响
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摘要
目的观察美托洛尔对老年男性心肌梗死病人外周血淋巴细胞G蛋白偶联受体激酶2(GRK2)表达的影响。方法选取65岁以上急性非ST段抬高型心肌梗死病人80例,分为对照组和美托洛尔组。对照组行常规治疗,美托洛尔组在常规治疗基础上应用美托洛尔,随访2年。分别于发病24 h内和治疗3、6、12、24个月时行心脏超声检查,并分别抽取外周血2 m L,分离淋巴细胞,提取RNA及蛋白,检测GRK2 mRNA和蛋白的表达水平。结果治疗前2组心脏超声各项指标、外周血淋巴细胞GRK2的表达无明显差异;治疗后,美托洛尔组GRK2表达逐渐降低,治疗12个月后GRK2表达水平明显低于对照组,而心脏射血分数则显著高于对照组。结论老年急性非ST段抬高型心肌梗死病人经美托洛尔治疗后,外周血淋巴细胞GRK2表达水平明显降低,心脏射血分数等指标无明显变化。随着疗程的增加,治疗效果越显著。
Objective To investigate the effect of metoprolol on the expression of G proteincoupled receptor kinases 2( GRK2) in the lymphocyte of the elderly patients with acute non-ST segment elevation myocardial infarction in male. Methods A total of 80 elderly male patients with acute nonST segment elevation myocardial infarction were divided into the control group and the metoprolol group,with 40 patients in each group. Conventional therapy was used in the control group,and metoprolol was used in the metoprolol group on the basis of conventional therapy. Cardiac function was evaluated by echocardiography,and the mRNA level and the protein level of GRK 2 in the peripheral blood lymphocytes were measured by qRT-PCR and Western blot at baseline,3,6,12,and 24 months after treatment. All patients were followed up for 2 years. Results There were no significant difference in the level of lymphocyte GRK2 and echocardiologic indicators between two groups at baseline; After treatment,GRK2 level in the metoprolol group was significantly lower than that in the control group 12 months after treatment,while the ejection fraction in the metoprolol group was significantly higher than that in the control group. Conclusions Metoprolol can inhibit the expression of GRK2 in lymphocyte of the elderly patients with acute non-ST segment elevation myocardial infarction.
Objective To investigate the effect of metoprolol on the expression of G proteincoupled receptor kinases 2( GRK2) in the lymphocyte of the elderly patients with acute non-ST segment elevation myocardial infarction in male. Methods A total of 80 elderly male patients with acute nonST segment elevation myocardial infarction were divided into the control group and the metoprolol group,with 40 patients in each group. Conventional therapy was used in the control group,and metoprolol was used in the metoprolol group on the basis of conventional therapy. Cardiac function was evaluated by echocardiography,and the mRNA level and the protein level of GRK 2 in the peripheral blood lymphocytes were measured by qRT-PCR and Western blot at baseline,3,6,12,and 24 months after treatment. All patients were followed up for 2 years. Results There were no significant difference in the level of lymphocyte GRK2 and echocardiologic indicators between two groups at baseline; After treatment,GRK2 level in the metoprolol group was significantly lower than that in the control group 12 months after treatment,while the ejection fraction in the metoprolol group was significantly higher than that in the control group. Conclusions Metoprolol can inhibit the expression of GRK2 in lymphocyte of the elderly patients with acute non-ST segment elevation myocardial infarction.
引文
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[8] Trappanese DM,Liu Y,McCormick RC,et al. Chronicβ1-adrenergic blockade enhances myocardialβ3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload:new insight into mechanisms of cardiac benefit with selectiveβ1-blocker therapy[J]. Basic Res Cardiol,2015,110(1):456.
[2] Santulli G,Campanile A,Spinelli L,et al. G proteincoupled receptor kinase 2 in patients with acute myocardial infarction[J]. Am J Cardiol,2011,107(8):1125-1130.
[3] Gao WQ,Han CG,Lu XC,et al. GRK 2 level in peripheral blood lymphocytes of elderly patients with acute myocardial infarction[J]. J Geriatr Cardiol,2013,10(3):281-285.
[4] Sato PY,Chuprun JK,Schwartz M,et al. The evolving impact of g protein-coupled receptor kinases in cardiac health and disease[J]. Physiol Rev,2015,95(2):377-404.
[5] Raake PW,Zhang XY,Vinge LE,et al. Cardiac G-proteincoupled receptor kinase2 ablation induces a novel Ca2+handling phenotype resistant to adverse alterations and remodeling after myocardial infarction[J]. Circulation,2012,125(17):2108-2118.
[6] Tian X,Wang Q,Guo R,et al. Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction[J].Neuropsychiatr Dis Treat,2016,12:2333-2341.
[7] White DC,Hata JA,Shah AS,et al.Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction[J].Proc Natl Acad Sci U S A,2000,97(10):5428-5433.
[8] Trappanese DM,Liu Y,McCormick RC,et al. Chronicβ1-adrenergic blockade enhances myocardialβ3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload:new insight into mechanisms of cardiac benefit with selectiveβ1-blocker therapy[J]. Basic Res Cardiol,2015,110(1):456.