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山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (5): 1-7.doi: 10.6040/j.issn.1671-7554.0.2016.1506

• 基础医学 •    下一篇

通心络对兔腹主动脉粥样硬化易损斑块中三维应变的影响

宋昱1,毛洋1,刘庆梅2,乔磊1,帖媛媛1,鲁璐3,张蕾1   

  1. 1.山东大学齐鲁医院心内科 教育部与卫生部心血管功能与重构重点实验室, 山东 济南 250012;2.新泰市第二人民医院介入治疗室, 山东 新泰 271200;3.济南市第四人民医院超声科, 山东 济南 250031
  • 收稿日期:2016-11-15 出版日期:2017-05-10 发布日期:2017-05-10
  • 通讯作者: 张蕾. E-mail:leilybao@163.com E-mail:leilybao@163.com
  • 基金资助:
    国家重点基础研究发展计划(973计划,2012CB518603);国家自然科学基金(60971023,81270351)

Effect of Tongxinluo on three-dimensional strain of atherosclerotic vulnerable plaque in rabbits

SONG Yu1, MAO Yang1, LIU Qingmei2, QIAO Lei1, TIE Yuanyuan1, LU Lu3, ZHANG Lei1   

  1. 1. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Second Peoples Hospital of Xintai, Xintai 271200, Shandong, China;
    3. Department of Ultrasound, Fourth Peoples Hospital of Jinan, Jinan 250031, Shandong, China
  • Received:2016-11-15 Online:2017-05-10 Published:2017-05-10

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摘要： 目的 在兔腹主动脉粥样易损斑块硬化模型中,以辛伐他汀作为阳性对照,进一步明确通心络对易损斑块三维应变的影响。 方法 50只纯种雄性新西兰大白兔行腹主动脉球囊拉伤,1%胆固醇饲料喂养10周,改为普通饲料继续喂养8周,并随机分为对照组、小剂量通心络组［0.15 g/(kg·d)］、中剂量通心络组［0.3 g/(kg·d)］、高剂量通心络组［0.6 g/(kg·d)］和辛伐他汀组［5 mg/(kg·d)］,每组10只。18周末采用酶法检测其血脂水平,并行体表三维超声及血管内超声检查,处死动物,取腹主动脉脱水,包埋制石蜡及冰冻切片,行苏木精-伊红染色、组织病理学染色以及免疫组织化学染色。 结果 在通心络和辛伐他汀药物干预下,中、大剂量通心络组及辛伐他汀组动脉粥样硬化斑块的周向(CSp)和轴向应变峰值(RSp)降低,而纵向应变峰值(LSp)升高,斑块面积和斑块负荷减小。同时,中、大剂量通心络及辛伐他汀干预可以减少斑块内巨噬细胞含量,降低斑块易损指数,并且减少斑块内基质金属蛋白酶2、9(MMP-2, MMP-9)的表达。 结论 通心络和辛伐他汀可通过抑制斑块内巨噬细胞含量及MMP-2、MMP-9表达影响斑块的三维应变,稳定动脉粥样硬化斑块,其稳定斑块作用可通过检测斑块三维应变进行无创监测。

关键词: 易损斑块, 三维应变, 基质金属蛋白酶, 通心络, 辛伐他汀

Abstract: Objective To investigate the effect and possible mechanism of Tongxinluo(TXL)and simvastatin on the three-dimensional strain of atherosclerotic vulnerable plaques. Methods After abdominal aortic balloon injury was induced, 50 male New Zealand rabbits were fed with 1% cholesterol diet for 10 weeks and then randomly assigned into 5 groups for 8-week ordinary treatment: control, low-dose TXL group ［0.15 g/(kg·d)］, moderate-dose TXL group ［0.3 g/(kg·d)］, high-dose TXL group ［0.6 g/(kg·d)］, and simvastatin group ［5 mg/(kg·d)］. At the end of week 18, longitudinal strain(LSp), circumferential(CSp)and radial(RSp)strain of plaques and intravenous 山 东 大 学 学 报 (医 学 版)55卷5期 -宋昱,等.通心络对兔腹主动脉粥样硬化易损斑块中三维应变的影响 \=-ultrasonograph were measured, and blood lipid analysis, pathologic and immunohistochemical staining were performed. Results With the treatment of TXL and simvastatin, CSp and RSp of plaques decreased, whereas LSp increased. Plaque area and burden reduced. Moderate and high dose of TXL and simvastatin intervention could reduce the number of macrophages, vulnerable index and the expressions of matrix metalloproteinase 2(MMP-2)and MMP-9 in plaques. Conclusion TXL and simvastatin modify the three-dimensional strain and enhance the stability of atherosclerotic vulnerable plaques by inhibiting the content of macrophages and expressions of MMP-2 and MMP-9. The plaque-stabilizing effect might be detected by noninvasive three-dimensional strain measurement.

Key words: Tongxinluo, Vulnerable plaque, Three-dimensional strain, Simvastatin, Matrix metalloproteinase

中图分类号: 

  • R541.4
[1] Xiao W, Jia Z, Zhang Q, et al. Inflammation and oxidative stress, rather than hypoxia, are predominant factors promoting angiogenesis in the initial phases of atherosclerosis[J]. Mol Med Rep, 2015, 12(3): 3315-3322.
[2] Michel JB, Martin-Ventura JL, Nicoletti A, et al. Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages[J]. Atherosclerosis, 2014, 234(2): 311-319.
[3] Finn AV, Nakano M, Narula J, et al. Concept of vulnerable/unstable plaque[J]. Arterioscler Thromb Vasc Biol, 2010, 30(7): 1282-1292.
[4] Lendon CL, Davies MJ, Richardson PD, et al. Testing of small connective tissue specimens for the determination of the mechanical behaviour of atherosclerotic plaques[J]. J Biomed Eng, 1993, 15(1): 27-33.
[5] Chan PS, Nallamothu BK, Gurm HS, et al. Incremental benefit and cost-effectiveness of high-dose statin therapy in high-risk patients with coronary artery disease[J]. Circulation, 2007, 115(18): 2398-2409.
[6] 郑博, 王新刚, 龚艳君, 等. 直接经皮冠状动脉介入治疗术前负荷剂量阿托伐他汀治疗对急性心肌梗死患者近期预后的影响[J]. 中国介入心脏病学杂志, 2013, 21(1): 41-45. ZHENG Bo, WANG Xingang, GONG Yanjun, et al. Impact of high loading-dose atorvastatin pre-treatment before primary percutaneous coronary intervention on coronary flow in patients with ST segment elevation myocardial infarction[J]. Chin J Intervent Cardiol, 2013, 21(1): 41-45.
[7] Ma L, Ni M, Hao PP, et al. Tongxinluo mitigates atherogenesis by regulating angiogenic factors and inhibiting vasa vasorum neovascularization in apolipoprotein E-deficient mice[J]. Oncotarget, 2016, 7(13): 16194-16204
[8] Zheng CY, Song LL, Wen JK, et al. Tongxinluo(TXL), a traditional Chinese medicinal compound, improves endothelial function after chronic hypoxia both in vivo and in vitro[J]. J Cardiovasc Pharmacol, 2015, 65(6): 579-586.
[9] Zhang L, Liu Y, Lu XT, et al. Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy[J]. Am J Physiol Heart Circ Physiol, 2009, 297(6): 2004-2014.
[10] Cannesson M, Tanabe M, Suffoletto MS, et al. Velocity vector imaging to quantify ventricular dyssynchrony and predict response to cardiac resynchronization therapy[J]. Am J Cardiol, 2006, 98(7): 949-953.
[11] Moreno PR, Falk E, Palacios IF, et al. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture[J]. Circulation, 1994, 90(2): 775-778.
[12] Ji QW, Guo M, Zheng JS, et al. Downregulation of T helper cell type 3 in patients with acute coronary syndrome[J]. Arch Med Res, 2009, 40(4): 285-293.
[13] Liu XQ, Mao Y, Wang B, et al. Specific matrix metalloproteinases play different roles in intraplaque angiogenesis and plaque instability in rabbits[J]. PLoS One, 2014, 9(9):107851. doi: 10.1371/journal.pone.0107851.
[14] 顾菲菲, 吕树铮, 陈韵岱, 等. 血管内超声技术对不稳定性心绞痛患者冠状动脉临界病变形态学评价[J]. 中国介入心脏病学杂志, 2011, 19(3): 125-128. GU Feifei, LÜ Shuzheng, CHEN Yundai, et al. Evaluation of plaque morphology of coronary borderline lesions in unstable angina patients by intravascular ultrasound[J]. Chin J Intervent Cardiol, 2011, 19(3): 125-128.
[15] Gijsen FJ, Wentzel JJ, Thury A, et al. Strain distribution over plaques in human coronary arteries relates to shear stress[J]. Am J Physiol Heart Circ Physiol, 2008, 295(4):1608-1614.
[16] 张梅. 动脉粥样硬化斑块无创性超声检测方法[J]. 中国医学前沿杂志(电子版), 2013, 5(4): 35-37.
[17] van der Wal AC, Becker AE. Atherosclerotic plaque rupture-pathologic basis of plaque stability and instability[J]. Cardiovasc Res, 1999, 41(2): 334-344.
[18] Waltenberger J. Pathophysiological bases of unstable coronary syndrome[J]. Herz, 2001, 26(Suppl 1): 2-8.
[19] Zhang L, Liu Y, Zhang PF, et al. Peak radial and circumferential strain measured by velocity vector imaging is a novel index for detecting vulnerable plaques in a rabbit model of atherosclerosis[J]. Atherosclerosis, 2010, 211(1): 146-152.
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