Ghrelin对心肌梗死大鼠恶性心律失常和早期左室重构的影响(英文)
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摘要
目的:本文主要研究ghrelin对心肌梗死大鼠恶性心律失常和早期左室重构的影响。方法:心肌梗死大鼠模型每天两次注射ghrelin(100μg/kg)或生理盐水。通过超声心动图评估大鼠的心脏重量并且观察大鼠的血流动力学。使用酶免疫分析法测定血清胰岛素生长因子I(IGF-1)、血浆肾上腺素、去甲肾上腺素和多巴胺的浓度。注射药物前后分析大鼠的神经功能。结果:与对照组相比,ghrelin治疗的心肌梗死模型大鼠生存率显著增加(P<0.05),心脏功能增强,但心肌梗死面积差异不大(P>0.05)。结论:Ghrelin能够提高心肌梗死模型大鼠的生存率、缓解心肌梗死大鼠心率失常、改善心肌梗死大鼠左心室重构。
Objective: To investigate the effects of ghrelin on the cardiovascular system in rats with myocardial infarction(MI),such as preventing malignant arrhythmia, delaying left ventricular remodeling and decreasing mortality. Methods: Ghrelin(100 μg/kg sc,twice daily) or saline were administered for 2 weeks from the day of MI operation in Wistar rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic and hemodynamic. Serum insulin-like growth factor I(IGF-I), plasma concentrations of epinephrine, norepinephrine, and dopamine were measured by using enzyme immunoassay kit. Before and after ghrelin(100 μg/kg sc)was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. Results: Results showed that compared with that in the control group rats, the percent survival of ghrelin treated rats increased significantly(P< 0.05), the cardiac function enhanced remarkably, but the size of the infarct of the left ventricular wall did not significantly differ between MI + NS rats and MI + Ghrelin rats(P> 0.05). Conclusions: Ghrelin can increase the survival rate, improve cardiac arrythmias and alleviate left ventricular remodeling of myocardial infarction rats.
Objective: To investigate the effects of ghrelin on the cardiovascular system in rats with myocardial infarction(MI),such as preventing malignant arrhythmia, delaying left ventricular remodeling and decreasing mortality. Methods: Ghrelin(100 μg/kg sc,twice daily) or saline were administered for 2 weeks from the day of MI operation in Wistar rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic and hemodynamic. Serum insulin-like growth factor I(IGF-I), plasma concentrations of epinephrine, norepinephrine, and dopamine were measured by using enzyme immunoassay kit. Before and after ghrelin(100 μg/kg sc)was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. Results: Results showed that compared with that in the control group rats, the percent survival of ghrelin treated rats increased significantly(P< 0.05), the cardiac function enhanced remarkably, but the size of the infarct of the left ventricular wall did not significantly differ between MI + NS rats and MI + Ghrelin rats(P> 0.05). Conclusions: Ghrelin can increase the survival rate, improve cardiac arrythmias and alleviate left ventricular remodeling of myocardial infarction rats.
引文
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[14]Okumura H,Nagaya N,Enomoto M,et al.Vasodilatory effect of ghrelin,an endogenous peptide from the stomach[J].J Cardiovasc Pharmacol,2002,39(6):779-783
[15]Yoon HJ,Jeong MH,Jeong Y,et al.Progressive dilation of the left atrium and ventricle after acute myocardial infarction is associated with high mortality[J].Korean Circ J,2013,43(11):731-738
[16]Nagaya N,Moriya J,Yasumura Y,et al.Effects of ghrelin administration on left ventricular function,exercise capacity,and muscle wasting in patients with chronic heart failure[J].Circulation,2004,110(24):3674-3679
[17]Toshinai K,Yamaguchi H,Sun Y,et al.Desacyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor[J].Endocrinology,2006,147(5):2306-2314
[2]Huang BS,Lee en FH.The brain renin-angiotensin-aldosterone system:a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction[J].Curr Heart Fail Rep,2009,6(2):81-88
[3]Tsukamoto T,Morita K,Naya M,et al.Decreased myocardialβ-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy[J].J Nucl Med,2007,48(11):1777-1782
[4]Lymperopoulos A,Rengo G,Gao E,et al.Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction[J].J Biol Chem,2010,285(21):16378-16386
[5]Carreira MC,Crujeiras AB,Andrade S,et al.Ghrelin as a GH-releasing factor[J].Endocr,2013:49-58
[6]Kim HH,Jeon TY,Park do Y,et al.Differential expression of ghrelin mRNA according to anatomical portions of human stomach[J].Hepatogastroenterology,2012,59(119):2217-2221
[7]Granata R,Isgaard J,Alloatti G,et al.Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone[J].Exp Biol Med(Maywood),2011,236(5):505-514
[8]Miller WL,Grill DE,Borlaug BA.Clinical features,hemodynamics,and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction:pulmonary hypertension and heart failure[J].JACC Heart Fail,2013,1(4):290-299
[9]Kusmic C,Barsanti C,Matteucci M,et al.Up-regulation of heme oxygenase-1 after infarct initiation reduces mortality,infarct size and left ventricular remodeling:experimental evidence and proof of concept[J].J Transl Med,2014,12(1):89
[10]Arvat E,Di Vito L,Broglio F,et al.Preliminary evidence that Ghrelin,the natural GH secretagogue(GHS)-receptor ligand,strongly stimulates GH secretion in humans[J].J Endocrinol Invest,2000,23(8):493-495
[11]Conti E,Andreotti F,Sciahbasi A,et al.Markedly reduced insulinlike growth factor-1 in the acute phase of myocardial infarction[J].J Am Coll Cardiol,2001,38(1):26-32
[12]Sarzi-Puttini P,Atzeni F,Schlmerich J,et al.Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor1(IGF1)resistance without influencing myoglobin and IGF1 binding proteins 1 and 3[J].Ann Rheum Dis,2006,65(3):301-305
[13]Berenguer-DaizéC,Boudouresque F,Bastide C,et al.Adrenomedullin blockade suppresses growth of human hormone-independent prostate tumor xenograft in mice[J].Clin Cancer Res,2013,19(22):6138-6150
[14]Okumura H,Nagaya N,Enomoto M,et al.Vasodilatory effect of ghrelin,an endogenous peptide from the stomach[J].J Cardiovasc Pharmacol,2002,39(6):779-783
[15]Yoon HJ,Jeong MH,Jeong Y,et al.Progressive dilation of the left atrium and ventricle after acute myocardial infarction is associated with high mortality[J].Korean Circ J,2013,43(11):731-738
[16]Nagaya N,Moriya J,Yasumura Y,et al.Effects of ghrelin administration on left ventricular function,exercise capacity,and muscle wasting in patients with chronic heart failure[J].Circulation,2004,110(24):3674-3679
[17]Toshinai K,Yamaguchi H,Sun Y,et al.Desacyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor[J].Endocrinology,2006,147(5):2306-2314