RhoA/ROCK信号通路与原发性高血压患者血压变异性及颈动脉内膜中层厚度的相关性

doi:10.6040/j.issn.1671-7554.0.2014.768

摘要/Abstract

摘要： 目的探讨原发性高血压患者血清RhoA激酶(ROCK)水平与血压变异性(BPV)及颈动脉内膜中层厚度(IMT)的关系.方法选取2013年9月至2014年8月山东大学附属济南市中心医院心内科原发性高血压患者73例,根据血清ROCK1水平分为高表达组(n=37)和低表达组(n=36).选取同期体检血压正常者40例为正常对照组.采用Human Rock1 Elisa kit及酶标仪检测血清ROCK1水平;监测24 h血压,记录24 h、白昼、夜间血压均值以及相应的血压标准差;采用彩色多普勒超声仪测量颈动脉IMT.结果高表达组和低表达组血清ROCK1水平明显高于正常对照组(P<0.01);高表达组24 h收缩压标准差(24hSSD)、日间收缩压标准差(dSSD)、夜间收缩压标准差(nSSD)均明显高于低表达组(P<0.05);高表达组和低表达组颈动脉IMT比正常对照组明显增厚,高表达组颈动脉IMT比低表达组明显增厚(P<0.05);血清ROCK1水平与24hSSD、dSSD、nSSD及颈动脉IMT呈显著正相关性(P<0.05).结论高血压患者血压变异性增高与RhoA/ROCK1信号通路高表达有关,RhoA/ROCK1信号通路过度激活可导致颈动脉IMT增厚及颈动脉粥样硬化斑块(AS)形成.

关键词: 动态血压监测, 动脉粥样硬化, 高血压, RhoA/ROCK, 血压变异性, 内膜中层厚度

Abstract: Objective To investigate the association of the blood pressure variability (BPV) and carotid intima-media thickness (IMT) with the Rho/ROCK signaling pathway in essential hypertensive patients. Methods A total of 73 hypertensive patients were divided into two groups based on serum level of ROCK1: group with high level of ROCK1 (n=37) and group with low level of ROCK1 (n=36), and 40 healthy subjects were selected as the control group. The serum level of ROCK1 was measured with Human Rock1 Elisa kit and microplate reader. The mean blood pressures (systolic and diastolic) and the standard deviations of 24 h, daytime and nighttime (24hSSD, dSSD, nSSD, 24hDSD, dDSD and nDSD) were monitored. The carotid artery IMT was determined with color Doppler ultrasound monitor. Results The serum level of ROCK1 in hypertensive group was higher than that of the control group (P<0.05). Compared with the group with low ROCK1 level, the 24hSSD, dSSD and nSSD were significantly increased in the group with high ROCK1 level (P<0.05). The carotid artery IMT in hypertensive patients was thicker than that of control group (P<0.05). The carotid artery IMT of the group with high ROCK1 level was thicker than that of the group with low ROCK1 level (P<0.05). The serum level of ROCK1 showed significant positive correlations with 24hSSD, dSSD, nSSD and carotid artery IMT in hypertensive patients (P<0.05). Conclusion The BPV is closely correlated with expression of Rho/ROCK signaling pathway in hypertensive patients. Overexpression of Rho/ROCK signalingpathway plays a key role in the progression of carotid artery IMT and atherosclerosis.

Key words: RhoA/ROCK, Intima-media thickness, Hypertension, Blood pressure variability, Atherosclerosis, Ambulatory blood pressure monitoring

中图分类号:

R544.1

徐忠阳, 王立启, 徐振兴, 赵乾, 朱世明. RhoA/ROCK信号通路与原发性高血压患者血压变异性及颈动脉内膜中层厚度的相关性[J]. 山东大学学报（医学版）, 2015, 53(2): 48-51.

XU Zhongyang, WANG Liqi, XU Zhenxing, ZHAO Qian, ZHU Shiming. Correlations among RhoA/ROCK signaling pathway, blood pressure variability and carotid artery intima-media thickness in essential hypertensive patients[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(2): 48-51.

参考文献

[1] 宫丽丽, 方莲花, 杜冠华. 心血管疾病治疗的新靶点—Rho激酶[J]. 中国药学杂志, 2008, 43(1):1-4.
[2] Wibberley A, Chen Z, Hu E, et al. Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle[J]. Br J Pharmacol, 2003, 138(5):757-766.
[3] Zhou Q, Gensch C, Liao JK. Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease[J]. Trends Pharmacol Sci, 2011, 32(3):167-173.
[4] Mueller BK, Mack H, Teusch N. Rho-kinase: a promising drug target for neurological disorders[J]. Nat Rev Drug Discov, 2005, 4(5):387-398.
[5] Gao HC, Zhao H, Zhang WQ, et al. The role of the Rho/Rock signaling pathway in the pathogenesis of acute ischemic myocardial fibrosis in rat models[J]. Exp Ther Med, 2013, 5(4):1123-1128.
[6] 蔡茜, 吴尚洁, 赵雪峰. 慢性阻塞性肺疾病相关性肺动脉高压患者外周血单核细胞Rho激酶水平测定[J]. 中南大学学报:医学版, 2012, 37(5):453-457. CAI Qian, WU Shangjie, ZHAO Xuefeng. Measurement of Rho-kinase in peripheral blood monocytes in patients with pulmonary arterial hypertension related to chronic obstructive pulmonary diseases[J]. J Cent South Univ:Med Sci, 2012, 37(5):453-457.
[7] Nakagawa O, Fujisawa K, Ishizaki T, et al. ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice[J]. FEBS Lett, 1996, 392(2):189-193.
[8] Somlyo AP, Somlyo AV. Ca²⁺ sensitivity of smooth muscle and nonmuscle myosin II; modulated by G proteins, kinases, and myosin phosphatase[J]. Physiol Rev, 2003, 83(4):1325-1358.
[9] Somlyo AP, Somlyo AV. Signal transduction by G proteins, Rhokinase and protein phosphatase to smooth muscle and non-musclemyosin II[J]. J Physiol, 2000, 522(2): 177-185.
[10] Mukai Y, Shimokawa H, Matoba T. Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension[J]. FASEB J, 2001, 15(6):1062-1064.
[11] Ito K, Hirooka Y, Sakai K, et al. Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system: possible involvement in neural mechanisms of hypertension[J]. Circ Res, 2003, 92(12):1337-1343.
[12] Mancia G, Grassi G. Mechanisms and clinical implications of blood pressure variability[J]. J Cardiovasc Pharmacol, 2000, 35(4):15-19.
[13] 胡建新, 胡宪珍, 张润香, 等. 血压变异性与血浆一氧化氮、内皮素含量的关系[J]. 江西医学院学报, 2004, 44(5):38-39. HU Jianxin, HU Xianzhen, ZHANG Runxiang, et al.The relationship between blood pressure variability and the plasma levels of nitric oxide and endothelin-1[J]. Acta Academiae Medicinae Jiangxi, 2004, 44(5):38-39.
[14] Shibasaki M, Durand S, Davis SL, et al. Endogenous nitric oxide attenuates neutrally mediated cutaneous vasoconstriction[J]. J Physiol, 2007, 585(2):627-634.
[15] Alexander J S. Rho, tyrosine kinase, Ca²⁺, and junctions in endothelial hyperpermeability[J]. Circ Res, 2000, 87(4):268-271.
[16] Worthylake RA, Lemoine S, Watson JM, et al. RhoA is required for monocyte tail retraction during transendothelial migration[J]. J Cell Biol, 2001, 154(1):147-160.
[17] 刘春南, 余首先, 赵晓宇. Rho激酶在心血管疾病中新进展及Rho激酶抑制剂的应用[J]. 心脏杂志, 2012, 24(4):521-524. LIU Chunnan, YU Shouxian, ZHAO Xiaoyu, et al. Rho kinase in cardiovascular diseases and applications for Rho kinase inhibition:Current progress[J]. Chin Heart J, 2012, 24(4):521-524.
[18] Sander D, Kukla C, Klingelhfer J, et al. Relationship between circadian blood pressure patterns and progression of early carotid atherosclerosis: A 3-year follow-up study[J]. Circulation, 2000, 102(13):1536-1541.

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