法舒地尔联合不同剂量瑞舒伐他汀对冠状动脉慢血流的影响

doi:10.12114/j.issn.1007-9572.2019.00.693

摘要/Abstract

摘要： 背景　随着冠状动脉造影的普及，冠状动脉慢血流（CSF）逐渐被重视。CSF可以导致急性冠脉综合征，甚至急性心肌梗死的发生。但是CSF发生的机制目前尚不明确。目的　观察法舒地尔联合不同剂量瑞舒伐他汀对CSF的影响。方法　选择2016年6月—2017年12月因胸痛就诊于河北医科大学第一医院且经冠状动脉造影诊断为CSF的患者作为研究对象，共117例入选。随机分为对照组（常规治疗），常规他汀组（常规治疗+法舒地尔+常规瑞舒伐他汀，常规组）和强化他汀组（常规治疗+法舒地尔+强化瑞舒伐他汀，强化组），各39例。观察治疗2周后3组患者心绞痛发作次数改善情况，评价各组心绞痛治疗总有效率。检测及比较治疗前、后超敏C反应蛋白（hs-CRP）、血清肿瘤坏死因子α（TNF-α）、白介素1（IL-1）、一氧化氮（NO）水平。治疗2周后行冠状动脉造影评估治疗后冠状动脉血流状态。结果　治疗2周后三组心绞痛治疗总有效率比较，差异有统计学意义（χ2=9.709，P=0.008），强化组心绞痛改善总有效率明显高于对照组，差异有统计学意义（χ2=9.047，P=0.003）。与本组治疗前相比，强化组和常规组hs-CRP、TNF-α、IL-1水平均明显降低（P<0.05），NO水平明显升高（P<0.05），对照组与治疗前相比无明显变化（P>0.05）；治疗后，强化组与常规组hs-CRP、TNF-α、IL-1水平低于对照组，NO水平高于对照组（P<0.05），但强化组与常规组比较，差异无统计学意义（P>0.05）。治疗后强化组及常规组各支冠状动脉血流速度均优于治疗前（P<0.05），且优于对照组（P<0.05），但强化组与常规组相比冠状动脉血流速度比较差异无统计学意义（P>0.05）。结论　在常规扩血管药物治疗基础上联用法舒地尔和瑞舒伐他汀，可有效改善CSF 患者冠状动脉血流速度，明显提高心绞痛治疗有效率，且常规剂量和强化剂量瑞舒伐他汀相比近期疗效无明显差异。

关键词: 冠状动脉慢血流, 瑞舒伐他汀, 法舒地尔

Abstract: Background　With the popularity of coronary angiography，coronary slow flow（CSF） has been paid more and more attention.CSF might lead to acute coronary syndrome and even acute myocardial infarction.However，the occurrence mechanism of CSF is still unclear.Objective　To observe the effects of fasudil combined with different doses of rosuvastatin on CSF.Methods　From June 2016 to December 2017，117 patients who sought healthcare due to chest pain in the First Hospital of Hebei Medical University and were diagnosed with CSF by coronary angiography were enrolled and were equally randomized into the control group（receiving routine treatment），normal dose group（receiving routine treatment plus fasudil and normal dose rosuvastatin） and high dose group（receiving routine treatment plus fasudil and high dose of rosuvastatin）.The number of attacks of angina pectoris，serum high-sensitivity C-reactive protein（hs-CRP），serum tumor necrosis factor-α（TNF-α），interleukin-1（IL-1），nitric oxide（NO），and coronary flow status measured by coronary angiography were compared before treatment and at the end of two-week treatment.The overall clinical response rate was also compared between the groups.Results　The overall response rate differed significantly between the groups（χ2=9.709，P=0.008）.In particular，high dose group showed much higher overall response rate compared with the control group（χ2=9.047，P=0.003）.Serum hs-CRP，TNF-α，and IL-1 decreased while NO increased obviously in normal and high dose groups after treatment（P<0.05），but these four parameters showed insignificant changed in the control group（P>0.05）.The levels of hs-CRP，TNF-α，IL-1 were lower but the level of NO was higher in both normal and high dose groups than the control group（P<0.05），There were no significant differences in post-treatment levels of hs-CRP，TNF-α，IL-1 and NO between the normal dose group and the high dose group（P>0.05）.The blood flow velocity in all coronaries improved significantly in both normal and high dose groups after treatment（P<0.05），and the improvement in both normal and high dose groups was better than the control group（P<0.05），and the improvement was similar in both groups（P>0.05）.Conclusion　Routine vasodilator therapy in combination with fasudil and rosuvastatin may effectively improve the coronary blood flow velocity，and the response rate in angina pectoris.However，use of normal or high dose of rosuvastatin may be not associated with significant changes in short-term efficacy for CSF.

Key words: Coronary slow flow, Rosuvastatin, Fasudil

李立卓,郑梅,李伟聪,等. 法舒地尔联合不同剂量瑞舒伐他汀对冠状动脉慢血流的影响[J]. 中国全科医学, 2019, 22(34): 4251-4255. DOI: 10.12114/j.issn.1007-9572.2019.00.693.
LI Lizhuo,ZHENG Mei,LI Weicong, et al. Effects of Fasudil and Different Doses of Rosuvastatin on Coronary Slow Flow　[J]. Chinese General Practice, 2019, 22(34): 4251-4255. DOI: 10.12114/j.issn.1007-9572.2019.00.693.

参考文献

［1］FINESCHI M，GORI T．Coronary slow-flow phenomenon or syndrome Y：a microvascular angina awaiting recognition［J］．J Am Coll Cardiol，2010，56（3）：239-240．DOI：10.1016/j.jacc.2009.09.082.
［2］MUTLUER F O，URAL D，GüNG?R B，et al．Association of interleukin-1 gene cluster polymorphisms with coronary slow flow phenomenon［J］．Anatol J Cardiol，2018，19（1）：34-41．DOI：10.14744/AnatolJCardiol.2017.8071.
［3］CAMSARI A，OZCAN T，OZER C，et al．Carotid artery intima-media thickness correlates with intravascular ultrasound parameters in patients with slow coronary flow［J］．Atherosclerosis，2008，200（2）：310-314．DOI：10.1016/j.athero- sclerosis.2007.12.028.
［4］SANTOS G L，HARTMANN S，ZIMMERMANN W H，et al．Inhibition of Rho-associated kinases suppresses cardiac myofibroblast function in engineered connective and heart muscle tissues［J］．J Mol Cell Cardiol，2019，134：13-28．DOI：10.1016/j.yjmcc.2019.06.015.
［5］李建军．他汀类药物非调脂作用及其机制（续9-1）［J］．中国循环杂志，2011，26（2）：155．DOI：10.3969/j.isma.1000-3614.2011-02-021.http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgxhzz201102024.
［6］GIBSON C M，SCHOMIG A．Coronary and myocardial angiograph：angiographic assessment of both epicardial and myocardial perfusion［J］．Circulation，2004，109（25）：3096-3105．DOI：10.1161/01.CIR.0000134278.50359.CB.
［7］LEUNG T，MANSER E，TAN L，et al．A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes［J］．J Biol Chem，1995，270（49）：29051-29054．DOI：10.1074/jbc.270.49.29051.
［8］NAKAMURA K，NISHIMURA J，HIRANO K，et al．Hydroxyfasudil，an active metabolite of fasudil hydrochloride，relaxes the rabbit basilar artery by disinhibition of myosin light chain phosphatase［J］．J Cereb Blood Flow Metab，2001，21（7）：876-885．DOI：10.1097/00004647-200107000-00013.
［9］WOLFRUM S，DENDORFER A，RIKITAKE Y，et al．Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection［J］．Arterioscler Thromb Vasc Biol，2004，24（10）：1842-1847．DOI：10.1161/01.ATV.0000142813.33538.82.
［10］AHMED L A，DARWISH H A，ABDELSALAM R M，et al．Role of Rho kinase inhibition in the protective effect of fasudil and simvastatin against 3-nitropropionic acid-induced striatal neurodegeneration and mitochondrial dysfunction in rats［J］．Mol Neurobiol，2016，53（6）：3927-3938．DOI：10.1007/s12035-015-9303-2.
［11］HIGASHI M，SHIMOKAWA H，HATTORI T，et al．Long-term inhibition of Rho-kinase suppresses angiotensin Ⅱ-induced cardiovascular hypertrophy in rats in vivo：effect on endothelial NAD（P）H oxidase system［J］．Circ Res，2003，93（8）：767-775．DOI：10.1161/01.RES.0000096650.91688.28.
［12］MA G，BI S．Effect of rosuvastatin on vascular endothelial functions and inflammatory factors of patients with type 2 diabetes mellitus and coronary heart disease［J］．Exp Ther Med，2019，17（1）：332-336．DOI：10.3892/etm.2018.6923．
［13］KUMAR B，SHAH M A A，KUMAR R，et al．Comparison of atorvastatin and rosuvastatin in reduction of inflammatory biomarkers in patients with acute coronary syndrome［J］．Cureus，2019，11（6）：e4898．DOI：10.7759/cureus.4898.
［14］LAUFS U，LA FATA V，PLUTAKY J，et a1．Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors［J］．Circulation，1998，97（12）：1129-1135．DOI：10.1161/01.cir.97.12.1129.
［15］NOMA K，KIHARA Y，HIGASHI Y，et al．Striking crosstalk of ROCK signaling with endothelial function［J］．J Cardiol，2012，60（1）：1-6．DOI：10.1016/j.jjcc.2012.03.005.

[1]	尚葛础, 王潇永, 高燕. 瑞舒伐他汀钙联合二甲双胍通过调控葡萄糖转运蛋白4表达发挥对糖尿病大鼠肾脏的保护作用研究[J]. 中国全科医学, 2022, 25(18): 2291-2296.
[2]	谢艳辉，刘淑珍，祝万洁，宋恒良，肖明洋，张娟，万大国. 依那普利联合体外反搏治疗冠状动脉慢血流的临床疗效及其对炎性因子和血管内皮功能的影响研究[J]. 中国全科医学, 2018, 21(23): 2802-2807.