鞘磷脂合酶抑制剂对血管紧张素Ⅱ诱导的高血压小鼠心肌纤维化的影响

doi:10.3969/j.issn.1006-7795.2016.06.003

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (6): 731-735.doi: 10.3969/j.issn.1006-7795.2016.06.003

• 心血管疾病的病理生理机制 • 上一篇下一篇

鞘磷脂合酶抑制剂对血管紧张素Ⅱ诱导的高血压小鼠心肌纤维化的影响

范一帆¹, 齐丹¹, 刘佳馨², 杨新春¹

1. 首都医科大学附属北京朝阳医院心脏中心高血压病研究北京市重点实验室, 北京 100020;
2. 北京市顺义区医院心内科, 北京 101300

收稿日期:2016-10-03 出版日期:2016-12-21 发布日期:2016-12-16
通讯作者: 杨新春 E-mail:yxc6229@sina.com
基金资助:
国家自然科学基金青年项目（81200194），北京市自然科学基金面上项目（7122072），中国博士后科学基金特别资助（2012T50115）

Effect of sphingomyelin synthase inhibitor on angiotensinⅡ-induced cardiac fibrosis in hypertensive mice

Fan Yifan¹, Qi Dan¹, Liu Jiaxin², Yang Xinchun¹

1. Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing Key Laboratory of Hypertension, Beijing 100020, China;
2. Department of Cardiology, The Hospital of Shunyi District, Beijing 101300, China

Received:2016-10-03 Online:2016-12-21 Published:2016-12-16
Supported by:
This study was supported by National Natural Science Foundation of China (81200194), Natural Science Foundation of Beijing(7122072),China Postdoctoral Science Foundation Funded Project (2012T50115).

摘要/Abstract

摘要： 目的研究鞘磷脂合酶抑制剂D609对血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）诱导的心肌纤维化的影响。方法将雄性野生型C57BL/6J小鼠28只，采用随机数字表区组分组法分为对照组、D609组、AngⅡ组和AngⅡ+D609组，每组7只。通过持续皮下灌注AngⅡ建立高血压模型，2周后观察小鼠的血压变化，行心脏超声评估心脏结构和功能。采用HE与Masson染色观察心肌纤维化。使用ELISA方法测定小鼠血浆中炎性反应因子、肿瘤坏死因子（tumor necrosis factor-α，TNF-α）及白细胞介素（interleukin-6，IL-6）的浓度。结果与对照组小鼠比较，AngⅡ组小鼠血压出现显著升高和心肌肥厚，而且心肌纤维化明显增加，血浆中TNF-α及IL-6的浓度显著增加。与AngⅡ组比较，AngⅡ+D609组小鼠血压降低，心肌肥厚明显减轻，心肌及血管组织的胶原纤维沉积显著减少，且血浆TNF-α及IL-6的浓度显著降低。结论鞘磷脂合酶在高血压导致的心肌纤维化中可能发挥重要作用。

关键词: 高血压, 心肌纤维化, 鞘磷脂合酶

Abstract: Objective To study the role of sphingomyelin synthase inhibitor (D609) on angiotensin Ⅱ (AngⅡ)-induced cardiac fibrosis in hypertensive mice. Methods Totally 28 male C57BL/6J mice were randomly divided into 4 groups:Control group, D609 treatment group, AngⅡ-infusion group and AngⅡ+D609 treatment group. Two weeks later, blood pressure was measured and echocardiography was performed. Cardiac fibrosis was evaluated by HE and Masson staining. Plasma level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) was measured by ELISA. Results Compared with control group, AngⅡ-infusion group showed increased blood pressure, myocardial hypertrophy, cardial fibrosis and decreased plasma level of TNF-α and IL-6. Compared with AngⅡ group, AngⅡ+D609 group demonstrated that D609 could significantly decrease the blood pressure, reduce myocardial hypertrophy and cardiac fibrosis, and also attenuate inflammatory responses by decreasing plasma level of TNF-α and IL-6. Conclusion Sphingomyelin synthase may play an important role in AngⅡ-induced cardiac fibrosis.

Key words: hypertension, myocardial fibrosis, sphingomyelin synthase

中图分类号:

R544.1

范一帆, 齐丹, 刘佳馨, 杨新春. 鞘磷脂合酶抑制剂对血管紧张素Ⅱ诱导的高血压小鼠心肌纤维化的影响[J]. 首都医科大学学报, 2016, 37(6): 731-735.

Fan Yifan, Qi Dan, Liu Jiaxin, Yang Xinchun. Effect of sphingomyelin synthase inhibitor on angiotensinⅡ-induced cardiac fibrosis in hypertensive mice[J]. Journal of Capital Medical University, 2016, 37(6): 731-735.

参考文献

[1] Harvey A, Montezano A C, Lopes R A, et al. Vascular Fibrosis in aging and hypertension: molecular mechanisms and clinical implications[J]. Can J Cardiol, 2016, 32(5):659-668.
[2] Azibani F, Benard L, Schlossarek S, et al. Aldosterone inhibits antifibrotic factors in mouse hypertensive heart[J]. Hypertension, 2012, 59(6):1179-1187.
[3] Stegemann C, Pechlaner R, Willeit P, et al. Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study[J]. Circulation, 2014, 129(18):1821-1831.
[4] Jiang X C, Goldberg I J, Park T S. Sphingolipids and cardiovascular diseases: lipoprotein metabolism, atherosclerosis and cardiomyopathy[J]. Adv Exp Med Biol, 2011, 721:19-39.
[5] Wu Y, Li Y, Zhang C, et al. S100a8/a9 released by CD11b+Gr1+ neutrophils activates cardiac fibroblasts to initiate angiotensin Ⅱ-Induced cardiac inflammation and injury[J]. Hypertension, 2014, 63(6):1241-1250.
[6] Borodzicz S, Czarzasta K, Kuch M, et al. Sphingolipids in cardiovascular diseases and metabolic disorders[J]. Lipids Health Dis, 2015, 14:55.
[7] Fenger M, Linneberg A, Jorgensen T, et al. Genetics of the ceramide/sphingosine-1-phosphate rheostat in blood pressure regulation and hypertension[J]. BMC Genet, 2011, 12:44.
[8] Cantalupo A, Zhang Y, Kothiya M, et al. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure[J]. Nat Med, 2015, 21(9):1028-1037.
[9] Yogi A, Callera G E, Aranha A B, et al. Sphingosine-1-phosphate-induced inflammation involves receptor tyrosine kinase transactivation in vascular cells: upregulation in hypertension[J]. Hypertension, 2011, 57(4):809-818.
[10] Spijkers L J, van den Akker R F, Janssen B J, et al. Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide[J]. PLoS One, 2011, 6(7):e21817.
[11] Yeboah J, McNamara C, Jiang X C, et al. Association of plasma sphingomyelin levels and incident coronary heart disease events in an adult population: Multi-Ethnic Study of Atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2010, 30(3):628-633.
[12] Zheng H, Xie X, Xie N, et al. Sphingomyelin levels in nondipper and dipper hypertensive patients[J]. Exp Ther Med, 2014, 7(3):599-603.
[13] Yu L, Yang G, Weng X, et al. Histone methyltransferase SET1 mediates angiotensin Ⅱ-Induced endothelin-1 transcription and cardiac hypertrophy in mice[J]. Arterioscler Thromb Vasc Biol, 2015, 35(5):1207-1217.
[14] Liu J, Huan C, Chakraborty M, et al. Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice[J]. Circ Res, 2009, 105(3):295-303.
[15] Frieler R A, Mortensen R M. Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling[J]. Circulation, 2015, 131(11):1019-1030.

鞘磷脂合酶抑制剂对血管紧张素Ⅱ诱导的高血压小鼠心肌纤维化的影响

Effect of sphingomyelin synthase inhibitor on angiotensinⅡ-induced cardiac fibrosis in hypertensive mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	左颖婷, 吴寿岭, 陈朔华, 田雪, 胥芹, 张怡君, 张晓丽, 王安心. 糖代谢异常人群中不同高血压亚型的心脑血管疾病风险[J]. 首都医科大学学报, 2023, 44(1): 42-48.
[2]	杨柳青, 田红梅, 石汉平. 三种饮食模式与慢性疾病研究进展[J]. 首都医科大学学报, 2022, 43(2): 311-320.
[3]	柳瑾, 齐新, 齐延芳, 冯娇娇, 彭金玲. 天津社区老年高血压患者心血管疾病危险因素分析[J]. 首都医科大学学报, 2021, 42(5): 804-809.
[4]	张爽, 马向科, 刘思维. 高血压脑出血合并肺部感染危险因素分析及防治[J]. 首都医科大学学报, 2021, 42(4): 660-663.
[5]	谭静, 李静, 张迎花, 左雪冰. 冠状动脉早期粥样硬化症患者冠状动脉钙化的影响因素分析[J]. 首都医科大学学报, 2020, 41(6): 978-981.
[6]	诸国华, 孙希鹏, 唐桦, 华琦. 初发轻度高血压患者内皮功能与左心室肥厚的相关性研究[J]. 首都医科大学学报, 2019, 40(3): 369-373.
[7]	周亚群, 丁存涛, 孙希鹏, 李静, 华琦. 原发性高血压患者红细胞分布宽度、中性粒细胞/淋巴细胞比值与内皮功能关系的研究[J]. 首都医科大学学报, 2018, 39(2): 292-298.
[8]	李秀娜, 周玉杰. 北京通州台湖地区65岁以上高血压老人心理健康现况及影响因素研究[J]. 首都医科大学学报, 2018, 39(1): 112-119.
[9]	吕曼. 小剂量氢氯噻嗪联合厄贝沙坦治疗原发性高血压的临床观察[J]. 首都医科大学学报, 2018, 39(1): 148-152.
[10]	孙希鹏, 丁存涛, 周亚群, 朱玮玮, 谭静, 李静, 华琦. 松龄血脉康对轻度原发性高血压病人血压及糖脂代谢的影响[J]. 首都医科大学学报, 2017, 38(3): 381-385.
[11]	周亚群, 丁存涛, 孙希鹏, 李静, 朱玮玮, 华琦. 原发性高血压病人超敏C反应蛋白与血压及血管内皮功能关系的研究[J]. 首都医科大学学报, 2017, 38(3): 397-400.
[12]	丁存涛, 周亚群, 孙希鹏, 李静, 朱玮玮, 华琦. 糖脂代谢对原发性高血压病人血管内皮功能的影响[J]. 首都医科大学学报, 2017, 38(3): 401-405.
[13]	吴景欢, 卓勤, 田园, 马彦宁, 崔璐, 朴建华, 杨晓光. 汉族老年人高血压与瘦素受体基因rs1137100和rs1137101多态性的研究[J]. 首都医科大学学报, 2017, 38(3): 439-445.
[14]	李敬, 华琦, 刘建峰, 罗鸿宇, 朱玮玮. 原发性高血压患者左心房内径与红细胞分布宽度的关系[J]. 首都医科大学学报, 2015, 36(3): 405-409.
[15]	杨伟, 何婧瑜, 王艳玲, 谭静, 范振兴, 华琦. 乌拉地尔与硝酸甘油注射液在老年高血压合并糖尿病患者发作急性心力衰竭的临床有效性与安全性[J]. 首都医科大学学报, 2015, 36(1): 67-72.