阿托伐他汀對高血壓患者炎癥因子IL-8、IL-1β及IMT的干預作用

作者單位:650032 昆明,昆明醫(yī)科大學成都軍區(qū)昆明總醫(yī)院臨床學院、成都軍區(qū)昆明總醫(yī)院心血管內科

梁彥麗,王先梅

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阿托伐他汀對高血壓患者炎癥因子IL-8、IL-1β及IMT的干預作用

作者單位:650032 昆明,昆明醫(yī)科大學成都軍區(qū)昆明總醫(yī)院臨床學院、成都軍區(qū)昆明總醫(yī)院心血管內科

梁彥麗,王先梅

[摘要]目的探討阿托伐他汀鈣對高血壓患者白細胞介素-8(IL-8)、白細胞介素1β(IL-1β)及頸動脈內膜中層厚度(IMT)的作用。方法回顧性分析 2012年本院住院原發(fā)性高血壓患者150例,隨機分為實驗組、臨床組、對照組,實驗組給予阿托伐他汀鈣20 mg、硝苯地平控釋片30 mg；臨床組給予培哚普利8 mg、硝苯地平控釋片30 mg、阿托伐他汀鈣20 mg；對照組給予培哚普利8 mg,硝苯地平控釋片30 mg；3組均服藥半年。運用ELISA法測定應用藥物前后各組血清IL-8、IL-1β濃度；超聲測定用藥前后頸部血管IMT厚度。結果實驗組和臨床組IL-8、IL-1β濃度及IMT均低于對照組,臨床組較實驗組的IL-8、IL-1β及IMT下降(P<0.05)。結論阿托伐他汀可以降低高血壓患者炎癥因子IL-8、IL-1β表達的水平及IMT,培哚普利與阿托伐他汀聯(lián)合有加強抗炎作用。

[關鍵詞]高血壓；阿托伐他?。话准毎樗?；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,高血壓是慢性炎癥過程,炎癥反應對粥樣硬化斑塊的形成與脫落的病理生理過程起關鍵作用,而白細胞介素-8(IL-8)和白細胞介素1β(IL-1β)是重要的炎癥反應標志物[1]。頸動脈粥樣硬化的形成是一個漸進的過程,高血壓是其主要危險因子之一[2]。研究表明,隨著高血壓病變程度的劇增,粥樣硬化斑塊形成率漸增,表明血壓升高是頸動脈粥樣硬化斑塊形成的促進因子。內皮功能受到損傷,內中膜增厚,誘發(fā)或加劇動脈粥樣硬化[3]。阿托伐他汀是否能降低高血壓患者的炎性因子水平及對IMT的影響仍不十分清楚,本研究將探究阿托伐他汀干預高血壓患者后,其炎性因子及IMT的變化,為他汀類藥物防治高血壓患者的動脈粥樣硬化提供針對炎性因子的理論根據(jù)。

1資料與方法

1.1病例資料回顧性分析2012年在本院住院的原發(fā)性高血壓患者共150例,均符合我國2010年修訂的高血壓診斷標準:收縮壓≥140 mmHg,舒張壓≥90 mmHg。年齡40~60歲。排除繼發(fā)性高血壓、嚴重肝腎疾病、惡性腫瘤、糖尿病及其他系統(tǒng)疾病。根據(jù)患者就診順序編號,采用隨機數(shù)字表法分為實驗組、臨床組、對照組各50例,3組間一般臨床資料比較沒有統(tǒng)計學差異(P>0.05),具有可比性。已向患者或其監(jiān)護人履行過知情告知義務,并取得知情同意,本研究已得到醫(yī)院醫(yī)學倫理委員會的批準。

1.2治療方法實驗組給予阿托伐他汀鈣(輝瑞制藥有限公司,國藥準字J20030047)20 mg、硝苯地平控釋片30 mg；臨床組給予培哚普利8 mg,硝苯地平控釋片30 mg,阿托伐他汀鈣20 mg；對照組給予培哚普利8 mg,硝苯地平控釋片30 mg；3組均口服,1次/d,連續(xù)服用半年。

1.3檢測指標

1.3.1用ELISA檢測血IL-8和IL-1β濃度藥物治療和治療半年后,分別抽取受試者凌晨6點空腹血5~6 ml,1000 r/min離心5 min,分離血清,-20 ℃冰箱冷凍保存,采用ELISA法檢測IL-8和IL-1β濃度,嚴格按照檢測試劑盒說明書操作,試劑盒均購自北京百泰克生物技術有限公司.

1.3.2頸動脈IMT測量在我科彩超室進行頸動脈IMT測量,均由同一位超聲師檢查,采用美國PHILIP-IE33超聲診斷儀,探頭型號L11-3,頻率為11 MHz。檢查前受試者休息至少15 min,取仰臥位,雙肩墊枕,頭頸部盡量仰伸,頭轉向對側。自頸動脈起始處縱向掃查,順次檢測雙側頸總動脈、頸總動脈分叉、頸內動脈顱外段與頸外動脈。檢測指標有:頸動脈內徑、IMT及有無斑塊形成。以頸動脈分叉處為參照,朝頸總動脈的方向1 cm處為頸總動脈IMT的測量部位；朝頸內動脈的方向1 cm處為頸內動脈IMT的測量部位；朝頸外動脈的方向1 cm處為頸外動脈IMT的測量部位。各測量3次,取雙側每個部位測量值的平均值,取6個測量值的平均值,即為該患者的頸動脈IMT。IMT>0.85 mm為內膜增厚。

2結果

2.1各組血清IL-8和IL-1β檢測結果治療半年后,臨床組較實驗組的血清IL-8、IL-1β水平降低,且兩者均顯著低于對照組(P<0.05)。見表1。

表1　各組治療后血清IL-8和IL-1β檢測結果(n=50)

注:與本組治療前比較,①P<0.01；與治療半年后對照組比較,②P<0.05；與治療半年后實驗組比較,③P<0.05

2.2各組頸動脈IMT檢測結果治療半年后,臨床組的IMT低于實驗組的IMT,且兩者均顯著低于對照組,均有統(tǒng)計學意義(P<0.05)。見表1。

3討論

高血壓對心腦血管的損害可累及全身各個器官[4],最常累及心、腦、腎等器官。因此,對于高血壓的防治具有重要的意義。高血壓的病變程度與炎性反應因子,如IL-1β、IL-8具有相關性[5]。阿托伐他汀為羥基-3甲基戊二酰輔酶A(HMG-CoA)還原酶抑制劑,具備降低三酰甘油及血清膽固醇的雙重作用,且副作用小[6]。它可減少冠心病及腦卒中的發(fā)生風險,能通過其多效性發(fā)揮保護心腦作用[7],阿托伐他汀通過升高抗氧化系統(tǒng)酶的活性,促使脂質過氧化程度降低,從而改善機體氧化應激狀態(tài),改善內皮功能,延緩AS發(fā)展[8]。血管外膜損傷可導致新生內膜形成,致使P38MAPK連續(xù)激活,而阿托伐他汀可抑制P38MAPK激活,減輕血管外膜損傷所致新生內膜形成[9]。阿托伐他汀除了明顯的降脂功效外,還可減少膽固醇的合成,進而降低心血管事件的發(fā)生率[10]。

本研究采用阿托伐他汀及硝苯地平共同干預實驗組及臨床組,阿托伐他汀有降脂、降膽固醇及炎癥因子等突出作用,口服硝苯地平可維持血壓穩(wěn)定,臨床組在此基礎上加用培哚普利片,以驗證阿托伐他汀聯(lián)合培哚普利是否有加強降低炎癥因子的作用。

本研究用阿托伐他汀鈣20 mg干預高血壓患者半年,結果發(fā)現(xiàn),與未服用此藥的對照組相比,應用阿托伐他汀鈣的實驗組及臨床組的IL-8、IL-1β的水平均顯著下降；而臨床組較實驗組的IL-8、IL-1β的水平更進一步下降(P<0.05),說明阿托伐他汀能顯著降低高血壓患者IL-8及IL-1β的水平,而且與培哚普利合用可更加降低IL-8及IL-1β的水平,使炎癥反應減輕,從而起到穩(wěn)定動脈粥樣硬化斑塊的作用[11]。頸動脈是連接心腦兩個主要器官的主要動脈,是最易受累的動脈血管,故頸動脈粥樣硬化被用來反映全身AS病變的狀況[12]。頸部血管超聲檢測IMT,可以評估頸動脈粥樣硬化程度。彩色多普勒頸部血管超聲具有直觀、確切等優(yōu)點,是診斷冠心病新“金標準”[13],主要測量頸動脈狹窄程度及鑒別斑塊性質[14]。

綜上所述,阿托伐他汀不僅能降低高血壓患者的炎癥因子水平,而且可降低患者的IMT,可延緩AS的發(fā)展,應該更深入探究其防治高血壓病的機理,以更好地指導臨床用藥。

【參考文獻】

[1]Neri M,Bello S,Bonsignore A,et al.Myocardial expression of TNF-α,IL-1β,IL-6,IL-8,IL-10 and MCP-1 after a single MDMA dose administered in a rat model[J].Current Pharmaceutical Biotechnology,2010,11(5):413-420.

[2]Vigili de Kreutzenberg S,Coracina A,Volpi A,et al.Microang-iopathy is independently associated with presence,severity and composition of carotid atherosclerosis in type 2 diabetes[J].Nutrition,Metabolism and Cardiovascular Diseases,2011,21(4):286-293.

[3]Casalnuovo G,Gerdts E,de Simone G,et al.Arterial stiffness is associated with carotid atherosclerosis in hypertensive patients(the campania salute network)[J].American Journal of Hypertension,2012,25(7):739-745.

[4]Cooper-DeHoff RM,Gong Y,Handberg EM,et al.Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease[J].JAMA,2010,304(1):61-68.

[5]Loan-Lancaster J,Abu-Raddad E,Polzer J,et al.Double-blind,randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102,a neutralizing IL-1β antibody,in patients with type 2 diabetes[J].Diabetes Care,2013,36(8):2239-2246.

[6]Amarenco P,Callahan A,Campese VM,et al.Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL trial[J].Stroke,2014,54(3):114-117.

[7]Tikkanen MJ,Fayyad R,Faergeman O,et al.Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels[J].International Journal of Cardiology,2013,168(4):3846-3852.

[8]Brili S,Tousoulis D,Antonopoulos AS,et al.Effects of atorvastatin on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young subjects with successfully repaired coarctation of aorta[J].HEART,2012,98(4):325-329.

[9]Zhang L,Sui H,Liang B,et al.Atorvastatin prevents amyloid-β peptide oligomer-induced synaptotoxicity and memory dysfunction in rats through a p38 MAPK-dependent pathway[J].Acta Pharmacologica Sinica,2014,35(6):716-726.

[10]Baetta R,Granata A,Miglietta D,et al.Nitric oxide-donating atorva-statin attenuates neutrophil recruitment during vascular inflammation independent of changes in plasma cholesterol[J].Cardiovascular Drugs and Therapy,2013,27(3):211-219.

[11]Lee BJ,Huang YC,Chen SJ,et al.Effects of coenzyme Q10 supplementation on inflammatory markers(high-sensitivity C-reactive protein,interleukin-6,and homocysteine)in patients with coronary artery disease[J].Nutrition,2012,28(7):767-772.

[12]Rossi R,Nuzzo A,Olaru AI,et al.Endothelial function affects early carotid atherosclerosis progression in hypertensive postmenopausal women[J].Journal of Hypertension,2011,29(6):1136-1144.

[13] Nelson M,Isaacs F,Hassan S,et al.Prevalence of abnormal bloodflow patterns and effects of biochemistry and lifestyle factors on the major neck vessels in patients with multiple sclerosis in the western cape,south africa[J].Medical Technology SA,2014,28(1):26-33.

[14]L?nnebakken MT,Gerdts E,Pedersen OM.Femoral Pseudoa-neurysm with a communicating arteriovenous fistula a complication after percutaneous coronary intervention[J].Circulation,2012,126(11):161-164.

(收稿日期:2014-11-20)

文章編號1004-0188(2015)03-0258-03

doi:10.3969/j.issn.1004-0188.2015.03.010

中圖分類號R 544.1

文獻標識碼A