脑利钠肽对心力衰竭患者心血管保护作用的研究

摘要/Abstract

摘要： 心力衰竭(HF) 是众多心血管疾病发展的终末阶段, 神经体液紊乱及心室重构是HF 患者重要的病理生理改变。研究发现, HF 患者血浆脑利钠肽(BNP) 水平明显升高。BNP 主要由心室合成分泌,作为循环激素, BNP 通过利钠肽受体-鸟甘酸环化酶(NPR-cGMP) 系统, 可排钠、利尿, 扩张血管, 增强迷走神经活性及拮抗交感神经活性, 从而明显改善HF患者的血流动力学状态, 且不伴有血浆肾素活性的激活。BNP 还可作用于心脏, 具有抗心肌肥大、抗纤维化作用, 作为局部调节因子在心室重构中发挥重要作用。通过远距分泌及旁分泌或自分泌作用,BNP 在HF 的发展及预后中发挥重要保护作用。

关键词: 心力衰竭, 神经体液, 抗肥大, 抗纤维化, 鸟甘酸环化酶

Abstract: Heart failure(HF) is the end stage of many cardiovascular diseases. Both the neurohumor overactivation and ventricular remodeling are the critical pathophysiological processes of HF. It has been demonstrated that the serum level of brain natriuretic peptide (BNP) is elevated obviously in HF patients. As a circulatory hormone, BNP is mainly produced in cardiac ventricle. Through the natriuretic receptor (NPR)-cyclic guanosine monophosphate(cGMP) pathway, BNP performs the properties of natriuresis, diuresis, vasodilatation, enhancing vagal reflex and inhibiting sympathetic activity, which can improve the hemodynamic of HF without activation of plasma renin. It has been reported that BNP has effects of antihypertrophic and antifibrotic and plays a role in the antiventricular remodeling. In a word, BNP plays an important role of cardioprotection in the development and prognosis of HF though the local autocrine and /orparacrine ways.

Key words: heart failure, neurohumor, antihypertrophy, antifibrotic, cyclic guanosine monophosphate

中图分类号:

R541.6

朱小琴, 洪华山. 脑利钠肽对心力衰竭患者心血管保护作用的研究[J]. 中国临床药理学与治疗学, 2007, 12(11): 1211-1215.

ZHU Xiao-qin, HONG Hua-shan. Cardioprotective function of brain natriuretic peptide in patients with heart failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(11): 1211-1215.

参考文献

1 Bruneau BG, Piazza LA, de Bold AJ.BNP gene expression is specifically modulated by stretch-and ET-1 in a new model of isolated rat atria[J]. Am J Physiol, 1997; 273:H2678-H2686.
2 Nazario B, Hu RM, Pedram A, et al.Atrial and brain natriuretic peptides stimulate the produc-tion and secretion of C-type natriuretic peptide from bovine aortic endothelial cells[J]. J Clin Invest, 1995;95: 1151-1157.
3 Van der Zander K, Houben AJ, Kroon AA, et al.Nitric oxide and potassium channels are invol-ved in brain natriuretic peptide induced vasodilatation in man[J]. J Hypertens, 2002; 20:493-499.
4 Cataliotti A, Boerrigter G, Chen HH, et al.Differential actions of vasopeptidase inhibition versus angiotensin converting enzyme inhibitionon diuretic therapy in experimental congestive heart failure[J]. Circulation, 2002;105:639-644.
5 Chen HH, Lainchbury JG, Harty GJ, et al.Subcutaneous brain natriuretic peptide and acute vas-opeptidase inhibition maximizing the natriuretic peptide system in experimental heart failure[J]. Circulation, 2002;105:999-1003.
6 Almirez R, Protter AA.Clearance of human brain natriuretic peptide in rabbits; effect of the k-idney, the natriuretic peptide clearance receptor, and peptidase activity[J]. J Pharmacol Exp Ther, 1999; 289:976-980.
7 Yoshimura M, Yasue H, Morita E, et al.Hemodynamic, renal, and hormonal responses to brainnatriuretic peptide infusion in patients with congestive heart failure[J]. Circulation, 1991; 84: 1581-1588.
8 Chen HH, Grantharn JA, Schirger JA, et al.Subcutaneous administration of brain natriuretic peptide in experimental heart failure[J]. JACC, 2000;36: 1706-1712.
9 Cataliotti A, Boerrigter G, Costello-Boerrigter LC, et al.Brain natriuretic peptide enhances re-nal actions of furosemide and suppresses furosemide-induced aldosterone activation in experimental heart failure[J]. Circulation, 2004; 109:1680-1685.
10 Marcus LS, Hart D, Packer M, et al.Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A doubleblind, placebocontrol-led, randomized crossover trial[J]. Circulation, 1996; 94: 3184-3189.
11 Van der Zander K, Houben AJ, Kroon AA, et al.Effects of brain natriuretic peptide on forear-m vasculature: comparison with atrial natriuretic peptide[J]. Cardiovasc Res, 1999;44: 595-600.
12 Protter AA, Wallace AM, Ferraris VA, et al.Relaxant effect of human brain natriuretic peptide on human artery and vein tissue[J]. Am J Hypertens, 1996;9:432-436.
13 Houben AJ, KrekelsM, Schaper NC, et al.Microvascular effects of atrial natriuretic peptide (ANP) in man:studies during high and low salt diet[J]. Cardiovasc Res, 1998; 39: 442-450.
14 Supaporn T, Wennberg PW, Wei CM, et al.Role for the endogenous natriuretic peptide syste-m in the control of basal coronary vascular tone in dogs[J]. Clin Sci(Lond),1996; 90: 357-362.
15 Okumura K, Yasue H, Fujii H Kugiyama, et al.Effects of brain (B-type) natriuretic peptide oncoronary artery diameter and coronary hemodynamic variables in humans:comparison with effects on sy stemic hemodynamic variables[J]. J Am Coll Cardiol, 1995; 25:342-348.
16 Zellner C, Protter AA, Ko E, et al.Coronary vasodilator effects of BNP:mechanisms of action in coronary conductance and resistance arteries[J]. Am J Physiol, 1999; 276:H1049-H1057.
17 Brunner F, Wolkart G.Relaxant effect of c-type natriuretic peptide involves endothelium and nitric oxide-cGMP system in rat coronary microvasculature[J]. Cardiovasc Res, 2001; 51: 577-584.
18 Tei M, Horie M, Makita T, et al.Atrial natriuretic peptide reduces the basal level of cytosolic free Ca²+ in guinea pig cardiac myocytes[J]. Biochem Biophys Res Commun, 1990;167:413-418.
19 Lin X, Hanze J, Heese F, et al.Gene expression of natriuretic peptide receptors in myocardial cells[J]. Circ Res, 1995; 77:750-758.
20 Oliver PM, Fox JE, Rockman HA, et al.Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor[J]. A Proc Natl Acad Sci USA, 1997; 94: 14730-14735.
21 Calderone A, Thaik CM, Takahashi N, et al.Nitric oxide, atrialnatriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts[J]. J Clin Invest, 1998;101:812-818.
22 Orio T, Nishikimi T, Yoshihara F, et al.Inhibitory regulation of hypertrophy by endogenous at-rial natriuretic peptide in cultured cardiac myocytes[J]. Hypertension, 2000;35:19-24.
23 Edler B, Lohmann SM, Smolenski A, et al.Inhibition of calcineurin-NFAT hypertrophy signali-ng by cGMP-dependent protein kinase type I incardiacmyocytes[J]. Proc Natl Acad Sci USA, 2002; 99:11363-11368.
24 Bikat A, De Windt LJ, Zetsche B, et al.Local atrial natriuretic peptide signaling prevents hy-pertensive cardiac hypertrophy in endothelial nitricoxide synthase-deficient mice[J]. J Biol Chem, 2005; 280:21594-21599.
25 Ltwick R, van EickelsM, Skryabin BV, et al.Pressure-independent cardiac hypertrophy in micewith cardiomyocyte-restricted inactivation of the atrial natriuretic petide receptor guanylyl cyclase[J]. A J Clin Invest, 2003; 111: 1399-1407.
26 Masato kasahara M, Mukoyama M, Sugawara A, et al.Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation[J]. J Am Soc Nephrol, 2000; 11: 1691-1701.
27 Nishikimi T, Maeda N, Matsuoka H.The role of natriuretic peptides in cardio-protection[J]. Cardiaovasc Res, 2006;69: 318-328.
28 Kapoun AM, Liang F, O Young G, et al.B-type natriuretic peptide exerts broad functional o-pposition to transforming growth factor-beta in primaryhuman cardiac fibroblasts:fibrosis, myofi-broblast conversion, proliferation, and inflammation[J]. Circ Res, 2004; 94:453-461.
29 Yoshimura M, Nakamura S, Nakayama M, et al.Expression of aldosterone synthase gene in fa-iling human heart:quantitative analysis using modified realtime polymerase chain reaction[J]. J Clin EndocrinolMetab, 2002;87: 3936-3940.
30 Kasahara M, Mukoyama M, Sugawara A, et al.Ameliorated glomerular injury in mice overexp-ressing brain natriuretic peptide with renal ablation[J]. J Am Soc Nephrol, 2000;11: 1691-1701.
31 Thomas CJ, Head GA, Woods RL.Similar baroreflex bradycardic actions of atrial natriuretic p-eptide and B and C types of natriuretic peptides in conscious rats[J]. J Hypertens, 1999; 17: 801-806.
32 Thomas CJ, May CN, Sharma AD, et al.ANP, BNP and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep[J]. Am J Physiol Regul Integr Comp Physiol, 2001;280:R282-288.
33 Thomas CJ, Woods RL.Guanylyl-cy clase receptors mediate cardiopulmonary vagal reflex a-ctions of ANP[J]. Hypertension, 2003;41:279-285.
34 Brunner La, Rocca HP, Kaye DM, et al.Effects of intravenous brain natriuretic peptide on reg-ional sympathetic activity in patients with chronic heart failure as compared with healthy controlsubjects[J]. J Am Coll Cardiol, 2001;37:1221-1227.
35 Woods RL.Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic p-eptide a brief review[J]. Clin Exp Pharmacol Phy siol, 2004; 31:791-794.
36 Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure[J]. Circulation, 2005; 111:1487-1491.
37 Wang DJ, Dowling TC, Meadows D, et al.Nesiritide does not improve renal funct-ion in patients with chronic heart failure and worsening serum creatinine[J]. Circulation, 2004;110:1620-1625.

[1]	郝潇, 赵美, 王文静, 张飞飞, 刘惠良, 党懿, 李树仁, 齐晓勇. 钠-葡萄糖共转运体2抑制剂在急性心肌梗死应用研究进展[J]. 中国临床药理学与治疗学, 2023, 28(7): 824-831.
[2]	彭勇, 范剑峰, 熊旭华, 肖冬平, 高招波, 郑春华. 右旋糖酐铁片对合并铁缺乏的射血分数减低的心力衰竭患者的影响[J]. 中国临床药理学与治疗学, 2023, 28(2): 178-183.
[3]	陈玉林, 蒋虎刚, 王新强, 刘凯, 李应东, 安涛, 赵信科. 基于网络药理学和分子对接探讨芪参益心颗粒治疗射血分数保留型心力衰竭的作用机制[J]. 中国临床药理学与治疗学, 2023, 28(10): 1081-1092.
[4]	杨胜, 王德国. 沙库巴曲缬沙坦联合达格列净治疗射血分数减低型心力衰竭疗效及对血清cTnⅠ、BNP水平的影响[J]. 中国临床药理学与治疗学, 2022, 27(9): 1010-1015.
[5]	彭娟, 范琳琳, 李然宜, 李晓宇, 吕迁洲, 邹云增. 心力衰竭药物治疗的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(4): 373-381.
[6]	刘平, 邱博, 吴惠珍. 维利西呱治疗心力衰竭的药理作用与临床评价[J]. 中国临床药理学与治疗学, 2022, 27(2): 212-218.
[7]	徐永华, 施向红. 托拉塞米联合左卡尼汀治疗慢性心力衰竭的疗效分析[J]. 中国临床药理学与治疗学, 2021, 26(6): 647-652.
[8]	陈力方, 王博, 王维蓉. 组蛋白去乙酰化酶3在心血管疾病中的研究进展[J]. 中国临床药理学与治疗学, 2021, 26(1): 88-97.
[9]	范剑峰，方译，郑春华. 沙库巴曲缬沙坦钠治疗慢性心力衰竭患者的临床疗效分析[J]. 中国临床药理学与治疗学, 2019, 24(7): 810-814.
[10]	沈蕾，王柯柯，杨景柯，赵俊涛，孟祥光，袁义强. 心力衰竭治疗药物的表观遗传药理学进展[J]. 中国临床药理学与治疗学, 2019, 24(3): 343-349.
[11]	魏子寒，李栋博，元峥，陆颍，杨国杰. 沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究[J]. 中国临床药理学与治疗学, 2019, 24(1): 57-62.
[12]	黄霆，汪和贵. β受体-PKA-AKAP信号通路调控心力衰竭的研究进展[J]. 中国临床药理学与治疗学, 2018, 23(5): 592-596.
[13]	王世彪，王程毅，翁斌，郭晓峰，林海. 无创心输出量监测联合米力农在小儿重症肺炎并心力衰竭中的疗效对比观察及对脑钠肽水平的影响研究[J]. 中国临床药理学与治疗学, 2018, 23(12): 1402-1407.
[14]	刘玉，张颖，王安才. 重组人脑利钠肽对慢性收缩性心力衰竭合并利尿剂抵抗患者的疗效及对TNF-α、NPY的影响[J]. 中国临床药理学与治疗学, 2017, 22(7): 814-820.
[15]	伍长娟，汤天生. 振源胶囊辅助治疗慢性心力衰竭疗效及安全性的Meta分析[J]. 中国临床药理学与治疗学, 2017, 22(3): 299-304.