溶血磷脂酸预警进展性脑梗死的临床研究
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摘要
研究目的：
探讨血浆溶血磷脂酸(lysophosphatidic acid,LPA)水平在进展性脑梗死(progressive stroke,PS)患者的变化及在预警中的作用；为进展性脑梗死(PS)患者提供一种新的预警方法；成为缺血性脑血管病患者的常规检查方法之一。
对象与方法：
对象：选取2006年01月-2008年03月赤峰学院附属医院神经内科住院发病24小时以内住院的脑梗死患者200例。根据病情的发展在发病72h时分为进展性脑梗死组、非进展性脑梗死组。所有患者签署知情同意书,以保证研究过程的顺利进行。
方法：所有患者均在入院时、发病后24h、48h、72h应用美国国立卫生研究院卒中量表(NIHSS)进行神经功能评分；在各时间点测定血浆溶血磷脂酸水平；同时行头颅CT检查,以确定梗死灶的部位、大小；向患者及家属询问性别、年龄、吸烟、饮酒史；既往冠心病、糖尿病、高血压病史；记录入院当时的血压及体温。溶血磷脂酸的测定试剂盒(北京泰福仕科技开发公司),产品批号：国食药监械(准)字2005第3401451号,其余试剂为国产分析纯,试剂配置水为双蒸馏水。严格按试剂说明书操作,测定血浆溶血磷脂酸水平。此外还在入院时测定血糖、血脂(包括总胆固醇、甘油三酯、低浓度脂蛋白、高浓度脂蛋白)、纤维蛋白原、血小板。最后用SPSS13.0统计软件处理,两组比较时,计数资料以率表示,进行X2检验,计量资料以X±S表示,进行t检验,将两组每个时间点的血浆溶血磷脂酸水平进行对比,确定溶血磷脂酸是否预警进展性脑梗死的发生。
研究结果：
两组临床与影像学检查比较：两组间年龄、性别、吸烟、饮酒等差异无显著性意义(P>0.05)。两组患者的实验室指标比较血小板、LAP有显著性差异；
LPA水平与PS发生率：随着血浆LPA水平的升高,PS的发生率呈显著递增趋势,入院时测定LPA达7.0 umol／L以上者,全部发生进展；
发病不同时间点的LPA水平：进展性脑梗死组发病后血浆LPA水平在不同时间点均高于非进展性脑梗死组,差异有显著意义；
进展性脑梗死组血浆LAP水平与梗死灶部位的关系：进展性脑梗死皮质组患者发病后血浆LPA水平较皮质下组有所增高,但差异无显著性意义；
病情严重程度与血浆LPA相关性：进展性脑梗死组的重型组血浆溶血磷脂酸浓度高于轻、中型组；中型组血浆溶血磷脂酸浓度高于轻型组；
研究结论：
本研究显示发病24h内血浆溶血磷脂酸水平>7.0umol／L的患者全部发生进展性脑梗死,该值具有一定的预警意义,值得进一步研究。
进展性脑梗死组的LPA水平在发病24h内,发病24h,48h,72h均较非进展性脑梗死组高,从发病开始升高至发病48h达高峰,在48h时血浆溶血磷脂酸水平>5.0umol／L或超过正常值时,发生进展。LPA在该时间点具有预警意义。
进展性脑梗死不同梗死部位、梗死体积及不同严重程度的LPA比较,发现大梗死灶组、重型组LPA水平高于其他组。
研究意义：
为研究预警进展性脑梗死提供理论依据：为进展性脑梗死患者提供检查手段；为后续的干预研究提供理论支持；化验血浆溶血磷脂酸水平适合基层医院,应用方便,易于接受。
Objectives:
To evaluate the significance of pre-warning of Lysophosphatidic acid on the progressive stroke; Provide a new pre-warning methods for progressive stroke; LPA become a routine examination in patients ischemic stroke.
Object and Method:
Object:Select hospitalized patients with stroke in January 2007-in March 2008 at Department of Neurology Affiliated Hospital Chifeng Institute. Group progressive stroke and group non-progressive stroke as the growth of the disease.
Methods:First, score all patients at admission,24 hours after onset,48 hours,72 hours with the National Institutes of Health Stroke Scale(NIHSS),at the same time all patients underwent head CT to determine infarction lesion site,size.;asked about the gender, age, smoking and drinking history; previous coronary heart disease, diabetes, history of hypertension to patients and their families; Record blood pressure and body temperature at the time of admission. All patients were at admission,24 hours after onset,48 hours,72 hours LPA was extracted. Lysophosphatidic acid reagent kits purchased from Beijing to TaiFuShi Technology Development Corporation, and the remaining for domestic reagents, reagents configured for dual-distilled water, operation accordancing to instructions strictly In addition, determination blood glucose, blood lipids (including total cholesterol, triglycerides, low concentrations of lipoprotein, high concentrations of lipoprotein) fibrinogen, platelet. Finally using statistical software SPSS13.0 deal, when compared to the two groups,using X2 test for countdata and X±S for measurement data. Determine the relation of Lysophosphatidic acid in the progressive stroke.
The result:
Compare of clinical and imaging examination in two groups. Between the two groups of age, gender, smoking, alcohol consumption, was not significant (P> 0.05) were compared in patients with laboratory indicators,between the two groups of platelet and LAP has significant difference.
LPA levels and the incidence of PS incidence was significantly increase With the high of plasma LPA levels trend of admission when LPA is 7.0 ummol/L or more, all of the patient is progress.
Plasma LPA levels (umol/L)in different time were higher in progressive and complete stroke at 24 hours after onset of were higher, there is significant difference in the progressive syroke and complete stroke after onset of plasma levels of LPA levere at different time points (P<0.05, P<0.01, P<0.05).
The relationship between plasma LPA level and the infarct site. Plasma LPA levels is high in the cortex of patients than the subcortical group in progressive stroke group, but the difference was not significant.
Severity of disease associated with plasma LPA. Severity group LPA higher than that of light, medium group (P<0.05); medium group higher than that in mild group (P <0.05).
Conclusion:
This research shows that patients with cerebral infarction within 24h plasm lysophospholipids acid level>7.0 umol/L occur progressive, the value is early warning, deserves further study.
The level of lysophospholipids acid within 24h,24h,48h,72h, is higher in progressive stroke group compared with the non-progressive group, from onset to reach peak incidence 48h,, when plasma LPA were> 5.0 umol/L or more than normal in 48h, progressive is occur. At this point LPA is warning factor.
The comparison of LPA level with infarct size. infarct seriousness in PS,found LPA lever is higher than other groups.
Search significance:
Provide a theoretical basis for study pre-warning progressive stroke.; Provide medical examination for the progressive stroke patients.; Provide theoretical support.for subsequent intervention study; LPA is application to basic-level hospitals, easy to accept.
探讨血浆溶血磷脂酸(lysophosphatidic acid,LPA)水平在进展性脑梗死(progressive stroke,PS)患者的变化及在预警中的作用；为进展性脑梗死(PS)患者提供一种新的预警方法；成为缺血性脑血管病患者的常规检查方法之一。
对象与方法：
对象：选取2006年01月-2008年03月赤峰学院附属医院神经内科住院发病24小时以内住院的脑梗死患者200例。根据病情的发展在发病72h时分为进展性脑梗死组、非进展性脑梗死组。所有患者签署知情同意书,以保证研究过程的顺利进行。
方法：所有患者均在入院时、发病后24h、48h、72h应用美国国立卫生研究院卒中量表(NIHSS)进行神经功能评分；在各时间点测定血浆溶血磷脂酸水平；同时行头颅CT检查,以确定梗死灶的部位、大小；向患者及家属询问性别、年龄、吸烟、饮酒史；既往冠心病、糖尿病、高血压病史；记录入院当时的血压及体温。溶血磷脂酸的测定试剂盒(北京泰福仕科技开发公司),产品批号：国食药监械(准)字2005第3401451号,其余试剂为国产分析纯,试剂配置水为双蒸馏水。严格按试剂说明书操作,测定血浆溶血磷脂酸水平。此外还在入院时测定血糖、血脂(包括总胆固醇、甘油三酯、低浓度脂蛋白、高浓度脂蛋白)、纤维蛋白原、血小板。最后用SPSS13.0统计软件处理,两组比较时,计数资料以率表示,进行X2检验,计量资料以X±S表示,进行t检验,将两组每个时间点的血浆溶血磷脂酸水平进行对比,确定溶血磷脂酸是否预警进展性脑梗死的发生。
研究结果：
两组临床与影像学检查比较：两组间年龄、性别、吸烟、饮酒等差异无显著性意义(P>0.05)。两组患者的实验室指标比较血小板、LAP有显著性差异；
LPA水平与PS发生率：随着血浆LPA水平的升高,PS的发生率呈显著递增趋势,入院时测定LPA达7.0 umol／L以上者,全部发生进展；
发病不同时间点的LPA水平：进展性脑梗死组发病后血浆LPA水平在不同时间点均高于非进展性脑梗死组,差异有显著意义；
进展性脑梗死组血浆LAP水平与梗死灶部位的关系：进展性脑梗死皮质组患者发病后血浆LPA水平较皮质下组有所增高,但差异无显著性意义；
病情严重程度与血浆LPA相关性：进展性脑梗死组的重型组血浆溶血磷脂酸浓度高于轻、中型组；中型组血浆溶血磷脂酸浓度高于轻型组；
研究结论：
本研究显示发病24h内血浆溶血磷脂酸水平>7.0umol／L的患者全部发生进展性脑梗死,该值具有一定的预警意义,值得进一步研究。
进展性脑梗死组的LPA水平在发病24h内,发病24h,48h,72h均较非进展性脑梗死组高,从发病开始升高至发病48h达高峰,在48h时血浆溶血磷脂酸水平>5.0umol／L或超过正常值时,发生进展。LPA在该时间点具有预警意义。
进展性脑梗死不同梗死部位、梗死体积及不同严重程度的LPA比较,发现大梗死灶组、重型组LPA水平高于其他组。
研究意义：
为研究预警进展性脑梗死提供理论依据：为进展性脑梗死患者提供检查手段；为后续的干预研究提供理论支持；化验血浆溶血磷脂酸水平适合基层医院,应用方便,易于接受。
Objectives:
To evaluate the significance of pre-warning of Lysophosphatidic acid on the progressive stroke; Provide a new pre-warning methods for progressive stroke; LPA become a routine examination in patients ischemic stroke.
Object and Method:
Object:Select hospitalized patients with stroke in January 2007-in March 2008 at Department of Neurology Affiliated Hospital Chifeng Institute. Group progressive stroke and group non-progressive stroke as the growth of the disease.
Methods:First, score all patients at admission,24 hours after onset,48 hours,72 hours with the National Institutes of Health Stroke Scale(NIHSS),at the same time all patients underwent head CT to determine infarction lesion site,size.;asked about the gender, age, smoking and drinking history; previous coronary heart disease, diabetes, history of hypertension to patients and their families; Record blood pressure and body temperature at the time of admission. All patients were at admission,24 hours after onset,48 hours,72 hours LPA was extracted. Lysophosphatidic acid reagent kits purchased from Beijing to TaiFuShi Technology Development Corporation, and the remaining for domestic reagents, reagents configured for dual-distilled water, operation accordancing to instructions strictly In addition, determination blood glucose, blood lipids (including total cholesterol, triglycerides, low concentrations of lipoprotein, high concentrations of lipoprotein) fibrinogen, platelet. Finally using statistical software SPSS13.0 deal, when compared to the two groups,using X2 test for countdata and X±S for measurement data. Determine the relation of Lysophosphatidic acid in the progressive stroke.
The result:
Compare of clinical and imaging examination in two groups. Between the two groups of age, gender, smoking, alcohol consumption, was not significant (P> 0.05) were compared in patients with laboratory indicators,between the two groups of platelet and LAP has significant difference.
LPA levels and the incidence of PS incidence was significantly increase With the high of plasma LPA levels trend of admission when LPA is 7.0 ummol/L or more, all of the patient is progress.
Plasma LPA levels (umol/L)in different time were higher in progressive and complete stroke at 24 hours after onset of were higher, there is significant difference in the progressive syroke and complete stroke after onset of plasma levels of LPA levere at different time points (P<0.05, P<0.01, P<0.05).
The relationship between plasma LPA level and the infarct site. Plasma LPA levels is high in the cortex of patients than the subcortical group in progressive stroke group, but the difference was not significant.
Severity of disease associated with plasma LPA. Severity group LPA higher than that of light, medium group (P<0.05); medium group higher than that in mild group (P <0.05).
Conclusion:
This research shows that patients with cerebral infarction within 24h plasm lysophospholipids acid level>7.0 umol/L occur progressive, the value is early warning, deserves further study.
The level of lysophospholipids acid within 24h,24h,48h,72h, is higher in progressive stroke group compared with the non-progressive group, from onset to reach peak incidence 48h,, when plasma LPA were> 5.0 umol/L or more than normal in 48h, progressive is occur. At this point LPA is warning factor.
The comparison of LPA level with infarct size. infarct seriousness in PS,found LPA lever is higher than other groups.
Search significance:
Provide a theoretical basis for study pre-warning progressive stroke.; Provide medical examination for the progressive stroke patients.; Provide theoretical support.for subsequent intervention study; LPA is application to basic-level hospitals, easy to accept.
引文
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1. Birschel P,Ellul J,Barer D,on behalf of the European Progressing Stroke Study roup:prossing stroke:Towards an internationally agreed definition.Cerebrovasc Dis 2004;17(2-3)242-252.
2. Cautier JC,Strok MD in Progression 〔J〕.Stroke,1985,16:4.
3. Kelly PJ,Rosand J,Kistler JP,et al.Homocysteine MYHFR677C polymorphism,and risk of ischemic stroke:teults of a meta-analysis 〔J〕 Neurology,2002,59:529-536.
4. 伍期专《中华老年心脑血管疾病杂志》2003年4期第五卷第二期。
5. 伍期专.缺血性脑梗死血浆溶血磷脂酸的研究方法.北京大学学报医学版,200133(4)：361.
6. Haseruck N,Erl W,Pandy D,et al.The plaque lipid lysophosphatidic acidstimulates platelet activation and platelet monocyte aggregate formation in whole blood:i volvement of P2Y1 and P2Y12receptors.Blood,2004,103(7):2585.
7. Siess W,Zangl KJ,Essler M,et al.Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by midly oxi-dized low density, lipoprotein and accumulates in human atheroscle-rotic lesions[J].Proc Natl Acad Sci USA,1999,96:6931-6936.
8. iessW.Ather-and thrombogenic actions of lysophosphatidie acid and sphingosine-1-phosphate [J].Biochim Biophys Acta,2002,1582:204-215.
9. Retzer M,Essler M,Lysophosphatidic acid-induced platelet shape change proceeds via ho/Rho inase-mediated myosin light-chain and moesin phosphory-Iation[J].CellSignal,2000,12:645-648.
10.王拥军等。BNC指南
11.全国第四届脑血管病学术会议。脑梗死患者临床神经功能缺损程度评分标准(1995)[J]。中华神经杂志,1996,29：379-380.
12.王拥军等。长谷川智能量表,BNC指南,科学技术文献出版社,2002.
13.伍其专。溶血磷脂酸在心脑血管疾病诊断及病因学中的作用[J]。中华老年心脑血管病杂志,2003,5(2)：77-79.
14.中华神经科学会.中华神经外科学会.脑缺血疾病分类(1995)(J).中华神经科杂志,1996,29(6)：376.
15.李红云,纪晓军,裴海军等。进展性脑梗死中国外医学脑血管疾病分册。2002,13 (2) 132-135.
16. PullicinoP,NelsonRF,Kenall BE,et al.Small deep infarcts dingnosed on computed tomography [J].Neurology:1980,0:1090.
17. Siess W, Zangl KJ, Essler M, et al. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human athefosclerotic lesions [J]. Proc Natl Acad Sci USA,1999,96(12):6931-6936.
18. Gueguen G, Gaige B, Grevy JM, etal. Structure-activity analysis of the effects of lysophosphatidic acid on platelet aggregation[J]. Biochemistry,1999,38(26): 8440-8450.
19. Fourcade O,Simon MF,LittL,etal.Propofol inhibits human platelet aggregation induced by proinflammatory lipid mediators.Anosth Analg,2004,99(2):393-398.
20. Chung SM, Bae ON, Lim KM, et al. Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes. Arterioscler Thromb Vasc Biol,2007,27: 414-421.