阿司匹林对急性脑梗死患者血浆溶血磷脂酸影响的研究
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摘要
目的:主要探讨不同剂量阿司匹林对颈内动脉系统急性脑梗死患者血浆溶血磷脂酸的影响,从而为缺血性脑血管病的预防和干预提供依据。
方法:病例来源为自2007年3月1日～2008年5月30日菏泽市立医院神经内科病房收住的患者及门诊病人。共分为①治疗组:急性颈内动脉系统脑梗死患者共132例,年龄35-80岁,平均56.7±11.6岁。均符合第四届全国脑血管病会议修订的诊断标准,发病在48小时以内;神经系统症状和体征符合颈内动脉供血区脑梗死;头颅CT平扫排除脑出血。所有入组患者在48小时内首次给予阿司匹林300mg口服,后随机分为两组,分别给与两种不同剂量(75mg,150mg)阿司匹林口服。②对照组:另外同期选取正常健康查体者30例作为对照组,年龄在42-70岁,平均52.1±13.4岁。均采取空腹静脉血4 ml,对照组即刻抽血,治疗组分别于服药前、服药后7天、2周、4周采取。血标本放入离心机以3500转/分的速度离心10分钟后,吸取血浆1ml,作LPA浓度测定。并对治疗组患者应用欧洲卒中量表(ESS)进行功能转归评分。实验数据采用SPSS11.0统计软件进行统计分析。两组间均数比较采用t检验,多个样本均数比较采用单因素方差分析。
结果:
1.治疗组口服阿司匹林前LPA测定结果与健康对照组比较差异有统计学意义(P＜0.05)。
2.除2例患者因服用阿司匹林后出现胃肠道副作用而退出该研究外,阿司匹林75mg/qd治疗组、150mg/qd治疗组治疗后7天分别与用药前比较使LPA下降均有统计学意义(P＜0.05);其中,口服150mg治疗组较75mg治疗组使LPA下降有显著差异(P＜0.05)。两治疗组在4周时LPA测定结果比较无统计学意义(P＞0.05)。
3.对两治疗组患者分别进行ESS评分,在治疗2周时与治疗前相比均有明显改善,其中口服大剂量者改善更明显。4周后评分两剂量组改善无明显差异。
结论:
本研究结果表明,脑梗死患者急性期LPA升高明显,口服阿司匹林可降低血浆LPA含量,提示LPA增高与血小板的活化有密切联系,阿司匹林可能是通过抑制环氧化酶途径抑制了血小板活化从而使LPA下降。脑梗死2周后小剂量阿司匹林即可稳定控制LPA含量;阿司匹林治疗后患者功能明显改善,早期大剂量改善更明显,在4周时患者功能评分服用大剂量阿司匹林者与小剂量比较未见明显改善,这为脑梗死早期的二级预防寻找阿司匹林的最佳剂量提供了理论依据。
Objective:To observe the influence of different dose of aspirin to the LPA level in patients with acute internal carotid circulation infarction.And to provide the basis for the preservation and intervention of the ischemic cerebrovascular disease.
Methods:The patients resource was the patients with acute internal carotid circulation infarction in Heze Municipal Hospital neurological medicine department and the medical outpatients from 2007.3.1-2008.5.30.Then divided into two group①therapia group:132 patients with acute internal carotid circulation infarction,age 35-80 years old,average age 56.7±11.6s.All coincidence with the castigatory diagnostic criteria in the fourth nationwide congress,onset in 48 hours,verified by CT,the nervous system symptoms and signs were fit internal carotid circulation cerbral infarction.All Patients were randomly classified into two groups,within 48 hours,of which 66 were receiving 75mg/d(low-dose) aspirin tablet,and other 66 were receiving 150mg/d(high-dose) aspirin tablet.②30 cases normal healthy human adopted as control group,age 42-70 years old,average age 52.1±13.4s.They were not accompanied with important organ diseases such as heart、liver,especially ovary cancer.Took venous blood 4ml in specific days on an empty stomach,control group taken instantly,therapia group taken blood before taking aspirin and after taking 7days、2weeks、4weeks.The bloods were centrifuged for 10 minutes at 3500r/min.Took suction 1ml blood plasma to make LPA concentration measurement.Used ESS scoring the function turnover to the therapia group patients.All datas were analysed statistically by SPSS 11.0 statiatical software.One-way analysis of variance was adopted to compare multiple sample mean.The mean of the two sample were compared with t test.
Results:1.Plasma LPA level in the patients with acute internal carotid circulation infarction before taking aspirin rose significantly,which were (4.06±1.23μmol/L)versus the control(1.77±1.03μmol/L)(P＜0.05)
2.Except 2 cases stoping the study for the adverse reaction of aspirin,Patients with acute internal carotid circulation infarction took apirin 75mg/qd group or took aspirin 150mg/qd,group in 7days,the PLA levels were all reduced significantly,which was(2.70±1.42μmol/L )or(2.31±1.03μmol/L) versus the control (1.77±1.03μmol/L)(P＜0.05),among the total,the high-dose reduced significantly, which was(2.31±1.03μmol/L) versus the low-dose(2.70±1.42μmol/L)(P＜0.05).The LPA levels of the patients who took different doses of aspirin in 4weeks have no statistics significance(P＞0.05)。
3.Score the function to the two therapia groups patients use ESS.The score in 2weeks versus before overdose improve significantly,and 150mg/d group improve more obviously;the score in 4weeks have little difference.
conclusion:The results of this study showed that the LPA level rose obviously in patients with acute ischemic cerebrovascular disease,taking aspirin tablet could reduce the content of plasma LPA.Proved LPA increased in close contact with platelet activation,aspirin may be ways to inhibit COX-inhibiting platelet activation,and thus inhibit the platelet-activating to have a process of LPA generating.After cerbral infarction two weeks,low-dose aspirin could control the stability of the LPA content,which may be provide the base to looking for the optimal dose of cerebral infarction for the secondary prevention.
方法:病例来源为自2007年3月1日～2008年5月30日菏泽市立医院神经内科病房收住的患者及门诊病人。共分为①治疗组:急性颈内动脉系统脑梗死患者共132例,年龄35-80岁,平均56.7±11.6岁。均符合第四届全国脑血管病会议修订的诊断标准,发病在48小时以内;神经系统症状和体征符合颈内动脉供血区脑梗死;头颅CT平扫排除脑出血。所有入组患者在48小时内首次给予阿司匹林300mg口服,后随机分为两组,分别给与两种不同剂量(75mg,150mg)阿司匹林口服。②对照组:另外同期选取正常健康查体者30例作为对照组,年龄在42-70岁,平均52.1±13.4岁。均采取空腹静脉血4 ml,对照组即刻抽血,治疗组分别于服药前、服药后7天、2周、4周采取。血标本放入离心机以3500转/分的速度离心10分钟后,吸取血浆1ml,作LPA浓度测定。并对治疗组患者应用欧洲卒中量表(ESS)进行功能转归评分。实验数据采用SPSS11.0统计软件进行统计分析。两组间均数比较采用t检验,多个样本均数比较采用单因素方差分析。
结果:
1.治疗组口服阿司匹林前LPA测定结果与健康对照组比较差异有统计学意义(P＜0.05)。
2.除2例患者因服用阿司匹林后出现胃肠道副作用而退出该研究外,阿司匹林75mg/qd治疗组、150mg/qd治疗组治疗后7天分别与用药前比较使LPA下降均有统计学意义(P＜0.05);其中,口服150mg治疗组较75mg治疗组使LPA下降有显著差异(P＜0.05)。两治疗组在4周时LPA测定结果比较无统计学意义(P＞0.05)。
3.对两治疗组患者分别进行ESS评分,在治疗2周时与治疗前相比均有明显改善,其中口服大剂量者改善更明显。4周后评分两剂量组改善无明显差异。
结论:
本研究结果表明,脑梗死患者急性期LPA升高明显,口服阿司匹林可降低血浆LPA含量,提示LPA增高与血小板的活化有密切联系,阿司匹林可能是通过抑制环氧化酶途径抑制了血小板活化从而使LPA下降。脑梗死2周后小剂量阿司匹林即可稳定控制LPA含量;阿司匹林治疗后患者功能明显改善,早期大剂量改善更明显,在4周时患者功能评分服用大剂量阿司匹林者与小剂量比较未见明显改善,这为脑梗死早期的二级预防寻找阿司匹林的最佳剂量提供了理论依据。
Objective:To observe the influence of different dose of aspirin to the LPA level in patients with acute internal carotid circulation infarction.And to provide the basis for the preservation and intervention of the ischemic cerebrovascular disease.
Methods:The patients resource was the patients with acute internal carotid circulation infarction in Heze Municipal Hospital neurological medicine department and the medical outpatients from 2007.3.1-2008.5.30.Then divided into two group①therapia group:132 patients with acute internal carotid circulation infarction,age 35-80 years old,average age 56.7±11.6s.All coincidence with the castigatory diagnostic criteria in the fourth nationwide congress,onset in 48 hours,verified by CT,the nervous system symptoms and signs were fit internal carotid circulation cerbral infarction.All Patients were randomly classified into two groups,within 48 hours,of which 66 were receiving 75mg/d(low-dose) aspirin tablet,and other 66 were receiving 150mg/d(high-dose) aspirin tablet.②30 cases normal healthy human adopted as control group,age 42-70 years old,average age 52.1±13.4s.They were not accompanied with important organ diseases such as heart、liver,especially ovary cancer.Took venous blood 4ml in specific days on an empty stomach,control group taken instantly,therapia group taken blood before taking aspirin and after taking 7days、2weeks、4weeks.The bloods were centrifuged for 10 minutes at 3500r/min.Took suction 1ml blood plasma to make LPA concentration measurement.Used ESS scoring the function turnover to the therapia group patients.All datas were analysed statistically by SPSS 11.0 statiatical software.One-way analysis of variance was adopted to compare multiple sample mean.The mean of the two sample were compared with t test.
Results:1.Plasma LPA level in the patients with acute internal carotid circulation infarction before taking aspirin rose significantly,which were (4.06±1.23μmol/L)versus the control(1.77±1.03μmol/L)(P＜0.05)
2.Except 2 cases stoping the study for the adverse reaction of aspirin,Patients with acute internal carotid circulation infarction took apirin 75mg/qd group or took aspirin 150mg/qd,group in 7days,the PLA levels were all reduced significantly,which was(2.70±1.42μmol/L )or(2.31±1.03μmol/L) versus the control (1.77±1.03μmol/L)(P＜0.05),among the total,the high-dose reduced significantly, which was(2.31±1.03μmol/L) versus the low-dose(2.70±1.42μmol/L)(P＜0.05).The LPA levels of the patients who took different doses of aspirin in 4weeks have no statistics significance(P＞0.05)。
3.Score the function to the two therapia groups patients use ESS.The score in 2weeks versus before overdose improve significantly,and 150mg/d group improve more obviously;the score in 4weeks have little difference.
conclusion:The results of this study showed that the LPA level rose obviously in patients with acute ischemic cerebrovascular disease,taking aspirin tablet could reduce the content of plasma LPA.Proved LPA increased in close contact with platelet activation,aspirin may be ways to inhibit COX-inhibiting platelet activation,and thus inhibit the platelet-activating to have a process of LPA generating.After cerbral infarction two weeks,low-dose aspirin could control the stability of the LPA content,which may be provide the base to looking for the optimal dose of cerebral infarction for the secondary prevention.
引文
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3.张德太,李明慧.血栓前体蛋白测定在急性脑梗死早期诊断的意义.中国老年学杂志,2003,23(9):580-581。
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2.陈俊,何国厚,余绍祖,等.S-100蛋白的动态变化在急性脑梗死诊断及预后中的临床价值.脑与神经疾病杂志,2003,11(3):151-154。
3.张德太,李明慧.血栓前体蛋白测定在急性脑梗死早期诊断的意义.中国老年学杂志,2003,23(9):580-581。
4.Moolenaar WH.Lysophosphatidic acid,a multifunctional phospholipids messenger.J Biol Chem,1995,270(22):12949-12952.
5.Valet P,Pages C,Jeanneton O,et al.Alpha2-adrenergic receptor-mediated release of Lysophosphosphatidic acid by adipocytes.A paracrine signal for preadipocyte growth.J Clin Invest,1998,101(7):1431-1438.
6.Shen Z,Yan X.Phorbol 12-myristate 13-acetate Stimulates Lysophosphatidic acid secretion from ovarian and cervical cancer cell but not from breast or leukemia cell[J].Gynecol Oncol,1998,71(3):364-368.
7.Liliom K,Belinson J,Morton RE,et al.Growth factor-like phosphlipid generated after corneal injury.Am J Physiol,1998,274(4 pt 1):C 1065-1074.
8.Chen ZM,Sandercock P,Pan HC,et al.Indications for early aspirin use in acute ischemic stroke:A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial.On behalf of the CAST and IST collaborative groups.Stroke,2000,31(5):1240-1249.
9.Pages C,Simon M-F,Valet P,et al.Lysophosphatidic acid synthesis and release.Prostaglandins &other Lipid Mediat,2001,64(1-4):1-10.
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