阿托伐他汀对高血压患者炎症因子IL-8、IL-1β及IMT的干预作用

作者单位:650032 昆明,昆明医科大学成都军区昆明总医院临床学院、成都军区昆明总医院心血管内科

梁彦丽,王先梅



阿托伐他汀对高血压患者炎症因子IL-8、IL-1β及IMT的干预作用

作者单位:650032 昆明,昆明医科大学成都军区昆明总医院临床学院、成都军区昆明总医院心血管内科

梁彦丽,王先梅

[摘要]目的探讨阿托伐他汀钙对高血压患者白细胞介素-8(IL-8)、白细胞介素1β(IL-1β)及颈动脉内膜中层厚度(IMT)的作用。方法回顾性分析 2012年本院住院原发性高血压患者150例,随机分为实验组、临床组、对照组,实验组给予阿托伐他汀钙20 mg、硝苯地平控释片30 mg；临床组给予培哚普利8 mg、硝苯地平控释片30 mg、阿托伐他汀钙20 mg；对照组给予培哚普利8 mg,硝苯地平控释片30 mg；3组均服药半年。运用ELISA法测定应用药物前后各组血清IL-8、IL-1β浓度；超声测定用药前后颈部血管IMT厚度。结果实验组和临床组IL-8、IL-1β浓度及IMT均低于对照组,临床组较实验组的IL-8、IL-1β及IMT下降(P<0.05)。结论阿托伐他汀可以降低高血压患者炎症因子IL-8、IL-1β表达的水平及IMT,培哚普利与阿托伐他汀联合有加强抗炎作用。

[关键词]高血压；阿托伐他汀；白细胞介素；IMT

Interventioneffect of atorvastatin on inflammatory factors IL-8, IL-1β and IMT in patients with hypertension

Liang Yanli, Wang XianmeiDepartment of Cardiovascular Internal Medicine, School of Clinical Medicine, Kunming General Hospital of Chengdu Military Command, Kunming Medical University /Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan,650032, China

[Abstract]ObjectiveTo explore the effect of atorvastatin calcium on interleukin-8 (IL-8), interleukin 1β (IL-1β) and carotid artery intima-media thickness (IMT) in patients with hypertension.MethodsA retrospective analysis was made for 150 patients with primary hypertension to receive treatment in our hospital in 2012. The patients were divided randomly into the experimental group, clinical group, and control group. The experimental group was administered with atorvastatin calcium of 20 mg and Nifedipine Controlled Release Tablets of 30 mg; the clinical group was administered with perindopril of 8 mg, Nifedipine Controlled Release Tablets of 30 mg, and atorvastatin calcium of 20 mg; the control group wasadministeredwith perindopril of 8 mg and Nifedipine Controlled Release Tablets of 30 mg. The administeringperiods of three groups were all six months. ELISA method was used to determine the serum levels of IL-8 and IL-1β before and after the drug administration, and ultrasonographywas used to measure the IMT thickness of cervical vascular system before andafter theadministration.ResultsThe IL-8andIL-1β concentration and IMT in both experimental and clinical groups were lower than those in the control group, and the IL-8, IL-1β and IMT in the clinical group were lower than those in the experimental group (P<0.05). ConclusionAtorvastatin can reduce the expression levels of inflammatory cytokines IL-8, IL-1β and IMTin patients with hypertension, and perindopril combined with atorvastatin has a reinforced anti-inflammatory effect.

[Key words]hypertension; atorvastatin; interleukin; IMT

研究表明,高血压是慢性炎症过程,炎症反应对粥样硬化斑块的形成与脱落的病理生理过程起关键作用,而白细胞介素-8(IL-8)和白细胞介素1β(IL-1β)是重要的炎症反应标志物[1]。颈动脉粥样硬化的形成是一个渐进的过程,高血压是其主要危险因子之一[2]。研究表明,随着高血压病变程度的剧增,粥样硬化斑块形成率渐增,表明血压升高是颈动脉粥样硬化斑块形成的促进因子。内皮功能受到损伤,内中膜增厚,诱发或加剧动脉粥样硬化[3]。阿托伐他汀是否能降低高血压患者的炎性因子水平及对IMT的影响仍不十分清楚,本研究将探究阿托伐他汀干预高血压患者后,其炎性因子及IMT的变化,为他汀类药物防治高血压患者的动脉粥样硬化提供针对炎性因子的理论根据。

1资料与方法

1.1病例资料回顾性分析2012年在本院住院的原发性高血压患者共150例,均符合我国2010年修订的高血压诊断标准:收缩压≥140 mmHg,舒张压≥90 mmHg。年龄40~60岁。排除继发性高血压、严重肝肾疾病、恶性肿瘤、糖尿病及其他系统疾病。根据患者就诊顺序编号,采用随机数字表法分为实验组、临床组、对照组各50例,3组间一般临床资料比较没有统计学差异(P>0.05),具有可比性。已向患者或其监护人履行过知情告知义务,并取得知情同意,本研究已得到医院医学伦理委员会的批准。

1.2治疗方法实验组给予阿托伐他汀钙(辉瑞制药有限公司,国药准字J20030047)20 mg、硝苯地平控释片30 mg；临床组给予培哚普利8 mg,硝苯地平控释片30 mg,阿托伐他汀钙20 mg；对照组给予培哚普利8 mg,硝苯地平控释片30 mg；3组均口服,1次/d,连续服用半年。

1.3检测指标

1.3.1用ELISA检测血IL-8和IL-1β浓度药物治疗和治疗半年后,分别抽取受试者凌晨6点空腹血5~6 ml,1000 r/min离心5 min,分离血清,-20 ℃冰箱冷冻保存,采用ELISA法检测IL-8和IL-1β浓度,严格按照检测试剂盒说明书操作,试剂盒均购自北京百泰克生物技术有限公司.

1.3.2颈动脉IMT测量在我科彩超室进行颈动脉IMT测量,均由同一位超声师检查,采用美国PHILIP-IE33超声诊断仪,探头型号L11-3,频率为11 MHz。检查前受试者休息至少15 min,取仰卧位,双肩垫枕,头颈部尽量仰伸,头转向对侧。自颈动脉起始处纵向扫查,顺次检测双侧颈总动脉、颈总动脉分叉、颈内动脉颅外段与颈外动脉。检测指标有:颈动脉内径、IMT及有无斑块形成。以颈动脉分叉处为参照,朝颈总动脉的方向1 cm处为颈总动脉IMT的测量部位；朝颈内动脉的方向1 cm处为颈内动脉IMT的测量部位；朝颈外动脉的方向1 cm处为颈外动脉IMT的测量部位。各测量3次,取双侧每个部位测量值的平均值,取6个测量值的平均值,即为该患者的颈动脉IMT。IMT>0.85 mm为内膜增厚。

2结果

2.1各组血清IL-8和IL-1β检测结果治疗半年后,临床组较实验组的血清IL-8、IL-1β水平降低,且两者均显著低于对照组(P<0.05)。见表1。

表1　各组治疗后血清IL-8和IL-1β检测结果(n=50)

注:与本组治疗前比较,①P<0.01；与治疗半年后对照组比较,②P<0.05；与治疗半年后实验组比较,③P<0.05

2.2各组颈动脉IMT检测结果治疗半年后,临床组的IMT低于实验组的IMT,且两者均显著低于对照组,均有统计学意义(P<0.05)。见表1。

3讨论

高血压对心脑血管的损害可累及全身各个器官[4],最常累及心、脑、肾等器官。因此,对于高血压的防治具有重要的意义。高血压的病变程度与炎性反应因子,如IL-1β、IL-8具有相关性[5]。阿托伐他汀为羟基-3甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂,具备降低三酰甘油及血清胆固醇的双重作用,且副作用小[6]。它可减少冠心病及脑卒中的发生风险,能通过其多效性发挥保护心脑作用[7],阿托伐他汀通过升高抗氧化系统酶的活性,促使脂质过氧化程度降低,从而改善机体氧化应激状态,改善内皮功能,延缓AS发展[8]。血管外膜损伤可导致新生内膜形成,致使P38MAPK连续激活,而阿托伐他汀可抑制P38MAPK激活,减轻血管外膜损伤所致新生内膜形成[9]。阿托伐他汀除了明显的降脂功效外,还可减少胆固醇的合成,进而降低心血管事件的发生率[10]。

本研究采用阿托伐他汀及硝苯地平共同干预实验组及临床组,阿托伐他汀有降脂、降胆固醇及炎症因子等突出作用,口服硝苯地平可维持血压稳定,临床组在此基础上加用培哚普利片,以验证阿托伐他汀联合培哚普利是否有加强降低炎症因子的作用。

本研究用阿托伐他汀钙20 mg干预高血压患者半年,结果发现,与未服用此药的对照组相比,应用阿托伐他汀钙的实验组及临床组的IL-8、IL-1β的水平均显著下降；而临床组较实验组的IL-8、IL-1β的水平更进一步下降(P<0.05),说明阿托伐他汀能显著降低高血压患者IL-8及IL-1β的水平,而且与培哚普利合用可更加降低IL-8及IL-1β的水平,使炎症反应减轻,从而起到稳定动脉粥样硬化斑块的作用[11]。颈动脉是连接心脑两个主要器官的主要动脉,是最易受累的动脉血管,故颈动脉粥样硬化被用来反映全身AS病变的状况[12]。颈部血管超声检测IMT,可以评估颈动脉粥样硬化程度。彩色多普勒颈部血管超声具有直观、确切等优点,是诊断冠心病新“金标准”[13],主要测量颈动脉狭窄程度及鉴别斑块性质[14]。

综上所述,阿托伐他汀不仅能降低高血压患者的炎症因子水平,而且可降低患者的IMT,可延缓AS的发展,应该更深入探究其防治高血压病的机理,以更好地指导临床用药。

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(收稿日期:2014-11-20)

文章编号1004-0188(2015)03-0258-03

doi:10.3969/j.issn.1004-0188.2015.03.010

中图分类号R 544.1

文献标识码A