不同剂量硫酸氢氯吡格雷对脑梗死患者血流动力学指标及血清miR-191、miR-18a水平的影响

doi:10.3969/j.issn.1004-583X.2021.07.006

摘要/Abstract

摘要：

目的探讨脑梗死治疗中硫酸氢氯吡格雷剂量对血流动力学、微RNAs(miRs)表达及神经功能的影响。方法选取2018年1月-2020年1月收治的脑梗死患者60例,随机分为对照组及观察组(每组30例),两组均在常规治疗的基础上服用硫酸氢氯吡格雷,对照组给予低剂量(50 mg/次,1次/d),观察组给予常规剂量(75 mg/次,1次/d),比较两组治疗前后血流动力学、miR-191、miR-18a、美国国立卫生研究院卒中量表(NIHSS)评分以及不良反应。结果治疗28 d两组收缩期峰值流速、舒张末期血流速度、平均流速均比治疗前升高,且观察组高于对照组,搏动指数、阻力指标均比治疗前降低,且观察组低于对照组(均P<0.05);治疗28 d两组miR-191均比治疗前降低,且观察组低于对照组,两组miR-18a均比治疗前升高,且观察组高于对照组(均P<0.05);两组治疗后NIHSS评分低于治疗前, 且组间、不同时点间差异有统计学意义,剂量对NIHSS评分随时间变化的趋势有影响(均P<0.05);两组不良反应发生率差异无统计学意义(P>0.05)。结论常规剂量硫酸氢氯吡格雷有助于提高脑梗死患者脑血流量,影响功能性miRs的表达,改善神经功能,且不增加不良反应。

关键词: 脑梗死, 氯吡格雷, 血流动力学, 微RNAs, 预后, 不良反应

Abstract:

Objective To investigate the effects of different doses of clopidogrel bisulfate (CB) on hemodynamics, expression of microRNAs(miRs), and nerve function in cerebral infarction (CI).Methods A total of 60 CI patients admitted from Jan 2018 to Jan 2020 were randomly divided into the control group and observation group with 30 patients in each group. Both groups were given different doses of CB on the basis of conventional treatment, the control group was given low dose (50 mg each time, once a day), and the observation group was given regular dose (75 mg each time, once a day). Hemodynamics, miR-191, miR-18a, National Institutes of Health Stroke Scale (NIHSS) score and adverse reactions were compared before and after treatment in two groups.Results After 28 days of treatment, peak systolic velocity, end diastolic velocity and mean velocity in both groups increased significantly, and they were higher in observation group than in control group. Pulsatility index and resistance index in both groups decreased, and they were lower in observation group than in control group (all P<0.05). miR-191 in both groups decreased, and the index was lower in observation group than in control group. But, miR-18a in both groups increased, and the index was higher in observation group than in control group (all P<0.05). Compared with before treatment, NIHSS score in both groups showed decrease after treatment (P<0.05).NIHSS score had significant difference between groups and different time points. Different doses of CB could affect NIHSS score trend over time ( P<0.05). There were no significant difference in the incidence of adverse reactions between two groups (P>0.05).Conclusion Regular dose CB can improve cerebral blood flow for CI patients, which may affect the expression of functional miRs, improve neurological function, therefore, reduce adverse reactions.

Key words: cerebral infarction, clopidogrel, hemodynamics, microRNAs, prognosis, adverse reactions

中图分类号:

R743.33

陈礼龙, 刘务朝, 司秋艳, 张建平, 程荣, 吴权. 不同剂量硫酸氢氯吡格雷对脑梗死患者血流动力学指标及血清miR-191、miR-18a水平的影响[J]. 临床荟萃, 2021, 36(7): 608-611.

Chen Lilong, Liu Wuchao, Si Qiuyan, Zhang Jianping, Cheng Rong, Wu Quan. Effects of different doses of clopidogrel bisulfate on hemodynamic indexes and serum miR-191 and miR-18a levels in patients with cerebral infarction[J]. Clinical Focus, 2021, 36(7): 608-611.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.07.006

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I7/608

图/表 3

参考文献 20

[1]	郭静. 阿司匹林、硫酸氢氯吡格雷联合膳食干预治疗脑梗死患者的临床效果[J]. 中国医药导报, 2018,15(8):72-75.
[2]	Lorenzen JM, Haller H, Thum T. MicroRNAs as mediators and therapeutic targets in chronic kidney disease[J]. Nat Rev Nephrol, 2011,7(5):286-294. doi: 10.1038/nrneph.2011.26 pmid: 21423249
[3]	Chen J, Cui C, Yang X, et al. MiR-126 affects brain-heart interaction after cerebral ischemic stroke[J]. Transl Stroke Res, 2017,8(4):374-385. doi: 10.1007/s12975-017-0520-z URL
[4]	Du K, Zhao C, Wang L, et al. MiR-191 inhibit angiogenesis after acute ischemic stroke targeting VEZF1 [ J]. Aging, 2019,11(9):2762-2786.
[5]	Wang SS, Li YQ, Liang YZ, et al. Expression of miR-18a and miR-34c in circulating monocytes associated with vulnerability to type 2 diabetes mellitus and insulin resistance[J]. J Cell Mol Med, 2017,21(12):3372-3380. doi: 10.1111/jcmm.2017.21.issue-12 URL
[6]	中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志, 2018,51(9):666-682.
[7]	高君武, 陈治国, 刘海洋, 等. 丁苯酞联合拜阿司匹林、硫酸氢氯吡格雷治疗急性脑梗死患者临床疗效[J]. 临床军医杂志, 2020,48(8):973-974.
[8]	周亦, 宋丽艳, 唐甲凡, 等. 丁苯酞软胶囊联合硫酸氢氯吡格雷治疗急性期脑梗死的临床观察[J]. 血栓与止血学, 2018,24(1):60-61, 64.
[9]	孔伟, 韩晨阳. 阿加曲班联合氯吡格雷治疗急性后循环缺血性脑梗死的疗效观察[J]. 现代药物与临床, 2018,33(1):50-53.
[10]	蔡传萍, 金冬梅, 录欣欣, 等. 功能性电刺激治疗对脑梗死大鼠神经功能和缺血半暗带GSK-3β蛋白的影响[J]. 中国康复医学杂志, 2018,33(6):647-652.
[11]	徐炳东, 吴正懂, 麦鸿成, 等. 影像学损害与血流灌注不匹配脑梗死患者发病6~24 h血管内治疗疗效分析[J]. 中国神经精神疾病杂志, 2018,44(9):555-558.
[12]	冉志军, 张显军, 杨黎侠, 等. 氯吡格雷联合前列地尔用于急性脑梗死治疗的疗效观察[J]. 贵州医药, 2019,43(12):1944-1945.
[13]	张丽, 巩晓英, 王继恒, 等. 阿托伐他汀联合氯吡格雷及拜阿司匹林对进展性脑梗死患者颈动脉粥样硬化的疗效评价[J]. 贵州医药, 2019,43(12):1945-1947.
[14]	Martinez B, Peplow PV. MicroRNAs as diagnostic markers and therapeutic targets for traumatic brain injury[J]. Neural Regen Res, 2017,12(11):1749-1761. doi: 10.4103/1673-5374.219025 pmid: 29239310
[15]	Song Y, Li Z, He T, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124[J]. Theranostics, 2019,9(10):2910-2923. doi: 10.7150/thno.30879 URL
[16]	Gacoń J, Badacz R, Stępień E, et al. Diagnostic and prognostic micro-RNAs in ischaemic stroke due to carotid artery stenosis and in acute coronary syndrome: A four-year prospective study[J]. Kardiol Pol, 2018,76(2):362-369. doi: 10.5603/KP.a2017.0243 URL
[17]	Wu XQ, Tian XY, Wang ZW, et al. miR-191 secreted by platelet-derived microvesicles induced apoptosis of renal tubular epithelial cells and participated in renal ischemia-reperfusion injury via inhibiting CBS[J]. Cell Cycle, 2019,18(2):119-129. doi: 10.1080/15384101.2018.1542900 URL
[18]	Yang T, Song J, Bu X, et al. Elevated serum miR-93, miR-191, and miR-499 are noninvasive biomarkers for the presence and progression of traumatic brain injury[J]. J Neurochem, 2016,137(1):122-129. doi: 10.1111/jnc.13534 URL
[19]	Zhou H, Yang C, Bai F, et al. Electroacupuncture alleviates brain damage through targeting of neuronal calcium sensor 1 by miR-191a-5p after ischemic stroke[J]. Rejuvenation Res, 2017,20(6):492-505. doi: 10.1089/rej.2017.1920 URL
[20]	Yang Q, Wang X, Cui J, et al. Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia[J]. BMC Complement Altern Med, 2014,14(6):183-195. doi: 10.1186/1472-6882-14-183 URL

组别	例数	PSV(cm/s)		EDV(cm/s)		Vm(cm/s)		RI		PI
组别	例数	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d
观察组	30	65.28±6.83	84.29±7.24^*	27.89±5.29	36.83±5.82^*	41.48±6.92	54.34±8.27^*	0.84±0.13	0.51±0.15^*	0.93±0.48	0.42±0.23^*
对照组	30	64.53±6.64	75.35±6.89^*	27.43±5.53	31.57±5.46^*	41.97±6.35	48.59±7.90^*	0.81±0.17	0.67±0.17^*	0.97±0.43	0.65±0.25^*
t值		0.431	4.899	0.329	3.610	0.282	2.754	0.768	3.865	0.340	3.708
P值		0.668	<0.01	0.743	<0.01	0.779	0.008	0.446	<0.01	0.735	<0.01

组别	例数	PSV(cm/s)		EDV(cm/s)		Vm(cm/s)		RI		PI
组别	例数	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d	治疗前	治疗28 d
观察组	30	65.28±6.83	84.29±7.24^*	27.89±5.29	36.83±5.82^*	41.48±6.92	54.34±8.27^*	0.84±0.13	0.51±0.15^*	0.93±0.48	0.42±0.23^*
对照组	30	64.53±6.64	75.35±6.89^*	27.43±5.53	31.57±5.46^*	41.97±6.35	48.59±7.90^*	0.81±0.17	0.67±0.17^*	0.97±0.43	0.65±0.25^*
t值		0.431	4.899	0.329	3.610	0.282	2.754	0.768	3.865	0.340	3.708
P值		0.668	<0.01	0.743	<0.01	0.779	0.008	0.446	<0.01	0.735	<0.01

组别	例数	miR-191		miR-18a
组别	例数	治疗前	治疗28 d	治疗前	治疗28 d
观察组	30	1.79±0.42	1.13±0.34^*	0.68±0.27	0.96±0.24^*
对照组	30	1.82±0.45	1.48±0.37^*	0.64±0.32	0.79±0.22^*
t值		0.267	3.815	0.523	2.860
P值		0.790	<0.01	0.603	0.006

组别	例数	miR-191		miR-18a
组别	例数	治疗前	治疗28 d	治疗前	治疗28 d
观察组	30	1.79±0.42	1.13±0.34^*	0.68±0.27	0.96±0.24^*
对照组	30	1.82±0.45	1.48±0.37^*	0.64±0.32	0.79±0.22^*
t值		0.267	3.815	0.523	2.860
P值		0.790	<0.01	0.603	0.006

组别	例数	NIHSS评分
组别	例数	治疗前	治疗3 d	治疗7 d	治疗14 d	治疗28 d
观察组	30	16.83±5.13	13.24±3.47^*	11.37±2.53^*	10.33±2.55^*	7.94±2.18^*
对照组	30	17.24±5.21	14.38±3.72^*	13.30±2.48^*	11.65±2.34^*	9.82±2.29^*
组间		F=5.424 P=0.009
时点间		F=7.263 P=0.003
组间·时点间		F=4.963 P=0.011