不同剂量培哚普利对兔急性心肌梗死后内皮祖细胞及心功能的影响

doi:10.6040/j.issn.1671-7554.0.2016.288

摘要/Abstract

摘要： 目的探讨不同剂量培哚普利对兔急性心肌梗死(AMI)后外周循环内皮祖细胞(EPCs)的动员作用及心脏收缩功能的影响。方法建立兔心肌梗死模型,随机分为假手术组(n=7)、AMI组(n=6)、小剂量培哚普利组(n=6)和大剂量培哚普利组(n=6)。应用流式细胞技术分别检测1、3、7、14、28 d循环血中EPCs数量,并于模型建立28 d采用心脏多普勒超声技术测量每搏输出量(SV)、左心室射血分数(LVEF)和左心室短轴缩短率(LVFS),取梗死部位心肌组织行HE染色,观察各组心肌细胞的坏死及紊乱程度。结果 AMI后经培哚普利干预,兔循环血中EPCs水平显著升高,大剂量培哚普利组效果显著(P<0.05)。AMI 28 d,AMI组与假手术组相比较,LVFS、SV、LVEF显著减低,经培哚普利干预后各指标显著增高,大剂量培哚普利组增高显著(P<0.05)。AMI组、小剂量培哚普利组和大剂量培哚普利组EPCs与LVEF呈相关性(R=0.468, P=0.05)。HE染色显示,与假手术组相比,AMI组心肌细胞基本被瘢痕组织替代,且其间有较多淋巴细胞浸润,小剂量培哚普利组见少量固缩心肌细胞及较多瘢痕组织,细胞肿胀变性及紊乱程度减轻,大剂量培哚普利组改善更为明显,可见较多正常心肌细胞存在及少量瘢痕组织。结论培哚普利可促进兔AMI后外周循环血中EPCs动员,提高LVEF、LVFS、SV,改善心功能,降低心肌细胞坏死及紊乱程度,且大剂量培哚普利干预效果更为显著,心脏收缩改善程度可能与EPCs水平有一定相关性。

关键词: 心脏收缩功能, 内皮祖细胞, 急性心肌梗死, 心肌细胞紊乱程度, 培哚普利

Abstract: Objective To investigate the effects of different doses of perindopril on mobilization of endothelial progenitor cells(EPCs)and the impact on cardiac systolic function in rabbits with acute myocardial infarction(AMI). Methods Rabbit models of acute myocardial infarction were established and randomly divided into 4 groups: sham-operated group(n=7), AMI group(n=6), low dose perindopril group(n=6, 0.218 mg/kg of perindopril was given a day after the model of AMI was built), high dose perindopril group(n=6, 0.436 mg/kg of perindopril was given a day after the model of AMI was built). The number of EPCs in circulating blood on day 1, 3, 7, 14, and 28 was counted with flow cytometry. On day 28, the stroke volume(SV), left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were examined with cardiac Doppler ultrasound. The necrosis and disarrangement 山东大学学报 (医学版)55卷2期 -谈红,等.不同剂量培哚普利对兔急性心肌梗死后内皮祖细胞及心功能的影响 \=-of cardiomyocytes in each group was observed after HE staining of infarcted cardiac areas. Results After perindopril treatment, there were significant increases of EPCs level in AMI rabbits, especially in high perindopril dose group(P<0.05). On day 28, there were significant decreases of LVFS, SV and LVEF in AMI group compared with sham-operated group(P<0.05). LVFS, SV and LVEF significantly increased after perindopril treatment, especially in high perindopril dose group(P<0.05). There was correlation between EPCs level and LVEF in all groups(R=0.468, P=0.05). HE staining showed that the normal cardiomyocytes in AMI group were replaced by large numbers of scar tissues with lymphocyte infiltration. Small quantity of pycnosis cardiomyocytes and relatively more scar tissues were seen in low dose perindopril group, and the degree of necrosis and disarrangement was lower than that in AMI group. The changes were more obvious in high dose perindopril group, in which more normal cardiomyocytes and fewer scar tissues were observed. Conclusion Perindopril can promote the mobilization of EPCs, elevate LVEF, LVFS and SV, and improve cardiac systolic function in AMI rabbits. High dose of perindopril is more efficient. There is correlation between EPCs level and the improvement of cardiac systolic function.

Key words: Perindopril, Endothelial progenitor cells, Cardiac systolic function, Acute myocardial infarction, Degree of cardiomyocyte disarrangement

中图分类号:

R541.4

谈红,孟楠,晋群,苏莉,张夏晓,陈英剑,郝哲,刘晓红. 不同剂量培哚普利对兔急性心肌梗死后内皮祖细胞及心功能的影响[J]. 山东大学学报（医学版）, 2017, 55(2): 55-60.

TAN Hong, MENG Nan, JIN Qun, SU Li, ZHANG Xiaxiao, CHEN Yingjian, HAO Zhe, LIU Xiaohong. Effects of different doses of perindopril on endothelial progenitor cells and systolic cardiac function in rabbits with acute myocardial infarction[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(2): 55-60.

参考文献

[1] Wang CH, Verma S, Hsieh IC, et al. Enalapril increases ischemia inducedendothelial progenitor cell mobilization through manipulation of the CD26 system[J]. I Mol Cell Cardiol, 2006, 41(1): 34-43.
[2] 董安平, 韩克, 马爱群, 等. 兔心肌梗死模型的建立及心功能的超声评价[J]. 中国医学影像技术, 2003, 19: 964-966. DONG Anping, HAN Ke, MA Aiqun, et al. Rabbit model of myocardial infarction and its evaluation by transthoracic echocardiography[J]. Chin J Med Imaging Technol, 2003, 19: 964-966.
[3] 徐叔云. 药理实验方法学[M]. 北京: 人民卫生出版社, 2002: 1861.
[4] Ho TK, Shiwen X, Abraham, et al. Stromal-cell-derived factor-1(SDF-1)/CXCL12 as potential target of therapeutic angiogenesis in critical leg ischaemia[J]. Cardiol Res Pract, 2012: 143209-143216. doi: 10.1155/2012/143209.
[5] Bai X, Wang X, Xu Q. Endothelial damage and stem cell repair in atherosclerosis[J]. Vascul Pharmacol, 2010, 52(5-6): 224-229.
[6] Goldstein LJ, Gallagher KA, Bauer SM, et al. Endothelial progenitor cell release into circulation is triggered by hyperoxia induced increases in bone marrow nitric oxide[J]. Stem Cells, 2006, 24(10): 2309- 2318.
[7] Liesmaa I, Leskinen HK, Kokkonen JO, et al. Hypoxia- induced expression of bradykinin type-2 receptors in endothelial cells triggers NO production, cell migration, and angiogenesis[J]. J Cell Physiol, 2009, 221(2): 359-366.
[8] Aicher A, Heeschen C, Mildner- Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells[J]. Nat Med, 2003, 9(11): 1370- 1376.
[9] You D, Cochain C, Loinard C, et al. Combination of the angiotensin- converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats[J]. J Pharmacol Exp Ther, 2008, 325(3): 766-773.
[10] Min LJ, Mogi M, Iwanami J, et al. AngiotensinⅡtype 2 receptor deletion enhances vascular senescence by methyl methanesulfonate sensitive 2 inhibition[J]. Hypertension, 2008, 51(5): 1339-1344.
[11] Li H, Liu Q, Wang N, et al. Correlation of different NADPH oxidase homologues with late endothelial progenitor cell senescence induced by angiotensin II: effect of telmisartan[J]. Intern Med, 2011, 50(16): 1631-1642.
[12] Yung LM, Wong WT, Tian XY, et al. Inhibition of renin-angioten-sin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats[J]. PLoS One, 2011, 6(3): 17437-17448.
[13] Sakuta T, Morita Y, Satoh M, et al. Involvement of the renin-ang-iotensin system in the development of vascular damage in a rat model of arthritis: effect of angiotensin receptor blockers[J]. Arthritis Rheum, 2010, 62(5): 1319-1328.
[14] Cacciatore F, Bruzzese G, Vitale DF, et al. Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients[J]. Eur J Clin Pharmacol, 2011, 67(9): 877-883.
[15] 孙佳音, 翟琳, 叶嘉欣, 等. 培哚普利对急性心肌梗死伴2型糖尿病患者内皮祖细胞动员及预后的影响[J]. 上海医学, 2012, 35(3): 189-193. SUN Jiayin, ZHAI Lin, YE Jiaxin, et al. Effect of perindopril on mobilization of endothelial progenital cells and prognosis in patients with acute myocardial infarction an type 2 diabetes[J]. Shanghai Med J, 2012, 35(3): 189-193.
[16] 兰莉, 秦俭, 陈运贞, 等. 奥美沙坦酯对急性心肌梗死大鼠内皮祖细胞动员的影响[J]. 临床心血管病杂志, 2009, 25(2): 102-105. LAN Li, QIN Jian, Chen Yunzhen, et al. Effect of olmesartan medoxomil on endothelial progenital cells mobilization in rats with acute myocardial infarction[J]. J Clin Cardio(China), 2009, 25(2): 102-105.
[17] 周婉明, 唐良秋, 万槐斌, 等. 冠心病患者外周血内皮祖细胞数量与心功能的关系[J]. 岭南心血管病杂志, 2011(增刊1): 128-131. ZHOU Wanming, TANG Liangqiu, WAN Huaibin, et al. Relationship between number of peripheral blood endothelial progenital cells and heart failure in patients with coronary artery disease[J]. South China Journal of Cardiovascular Diseases, 2011(Suppl 1): 128-131.
[18] 赵子粼, 许顶立, 郭志刚, 等. 内皮祖细胞对心梗后心衰患者心功能改变的影响[J]. 南方医科大学学报, 2011, 31(3): 504-507. ZHAO Zilin, XU Dingli, GUO Zhigang, et al. Effect of granulocyte colony stimulating factor EPC on cardiac function in patients heart failure after myocardial infarction[J]. J South Med Univ, 2011, 31(3): 504-507.
[19] 陈伟, 谈红, 李晓燕, 等. 冠心病患者外周血内皮祖细胞数量差异及其对内皮功能的影响[J]. 山东大学学报(医学版), 2012, 50(8): 73-76. CHEN Wei, TAN Hong, LI Xiaoyan, et al. Quantity variance of endothelial progenitor cells in peripheral blood of patients with coronary heart disease and its influence on endothelial function[J]. Journal of Shandong University(Health Sciences), 2012, 50(8): 73-76.
[20] Tan H, Li X, Chen W, et al. Effects of losartan on the mobilization of endothelial progenitor cells and improvement of endothelial function[J]. Ann Clin Lab Sci, 2013, 43(4): 402-406.
[21] 谈红, 王雪, 李晓燕, 等. 培哚普利对冠心病患者循环血内皮祖细胞及血管内皮功能的影响[J].中国循环杂志, 2015, 30(1): 22-25. TAN Hong, WANG Xue, LI Xiaoyan, et al. Effect of different doses of perindopril on endothelial progenitor cells and vascular endothelial function in patients with coronary heart disease[J]. Chinese Circulation Journal, 2015, 30(1): 22-25.

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