冠心病急性冠脉综合征中医辨证分型与PAI-1、ACE2的相关性研究
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摘要
随着经济的发展,冠心病发病率逐渐上升,纤溶酶原激活物抑制剂-1(PAI-1)是组织特异性纤溶酶原激活剂(t-PA)和尿激酶型纤溶酶原激活剂(u-PA)的主要生理学抑制剂,在血栓的发生发展中起着重要的作用,ACE2是肾素-血管紧张素系统(RAS)的又一新成员,使传统的RAS系统更加复杂,研究证明ACE2与冠心病密切相关。随着检测技术的提高,中医的传统的诊断方法需要改进,需要注入新的技术和活力。
目的:
通过检测血清纤溶酶原激活物抑制剂-1(PAI-1)、ACE2水平,探讨血清PAI-1、ACE2水平与冠心病中医辨证分型、冠心病病变程度之间的相关性,为冠心病中西医结合的研究提供临床依据。
方法:
临床确诊并经过冠状动脉造影术(CAG)证实的急性冠脉综合征患者139例,正常对照组30例。急性冠脉综合征患者入院时收集一般资料、症状、体征、舌象、脉象等临床资料,进行辨证分型,其中心血瘀阻31例;痰阻心脉47例,;心肾阴虚33例;阳气虚衰28例。根据CAG结果进行病变范围分组,分为单支病变组、双支病变组、多支病变组。正常对照组30例。收集所有研究对象的一般资料,并收集患者入院相关检查指标如:心电图、心脏彩超、心肌酶谱等,患者术前留取空腹血4ml,所有标本在室温下静置1-2小时待血清析出,然后用离心机离心20min(3000r/min),将上清转移至Ependorf管,放置在-70℃冰箱保存,最后统一用酶联免疫吸附法(ELISA)法检测血清PAI-1、ACE2水平。统计采用方差分析、t或t'检验进行冠心病组与正常对照组、各中医辨证分型组、各病变范围组各检测指标的两两比较或直线相关分析。
结果:
1.冠心病组与正常对照组一般资料分析发现,冠心病组除高密度脂蛋白低于正常对照组外,其余指标如体重指数(BMI)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、PAI-1及ACE2水平均高于正常对照组,其中,TC、TG、ACE2有统计学差异(p＜0.05);
2.三支病变组的血清PAI-1、ACE2水平以及年龄、LDL-C、TG、冠脉积分高于单支病变和双支病变组,但只有年龄、冠脉积分有统计学差异;
3.ACE2与冠脉积分呈正相关;PAI-1未发现其相关性;年龄与冠脉积分呈正相关;
4.在不同性别之间,未发现PAI-1、ACE2及冠脉病变严重程度之间有差异;
5.各中医辨证分型与正常对照组之间相比,TC、TG、ACE2水平高正常对照组,有统计学差异,但各证型间无发现统计学差异;
结论:
1.冠心病组血清PAI-1、ACE2水平显著高于正常对照组,具有一定的临床意义;
2.血清PAI-1水平受多种因素影响,临床上需综合考虑;
3.血清ACE2水平可作为ACS的发病危险因素及检测指标之一;
4.血清PAI-1水平与冠脉病变严重程度无明显相关性,ACE2水平与冠脉严重程度的相关性需进一步观察;
5.中医辨证分型不能评估冠脉病变的严重程度;
6.中医辨证分型各组之间,血清PAI-1、ACE2水平无显著差异,不能为冠心病中医现代化辨证分型提供依据。
With the development of economy,there is a gradual increase in the incidence of coronary heart disease,plasminogen activator inhibitor -1(PAI-1) is the main physiological inhibitor of tissue-specific plasminogen activator(t-PA) and urokinase -type plasminogen plasminogen activator(u-PA),PAI-1 plays an important role in the occurrence and development of thrombosis;ACE2 is a new member of the renin - angiotensin system(RAS),it makes the traditional system of RAS more complex.What's more,the study have proved that ACE2 is closely related with coronary heart disease.With the improvement of detection technology,the traditional Chinese medicine diagnosis methods need to be improved and injected new technology and vitality.
Objective:
Through testing the serum fibrinolytic enzyme activator inhibitors - 1(PAI-1),ACE2,we may explore the correlation among the level of PAI-1 and ACE2,TCM syndrome of coronary heart disease and the severity of coronary artery,then provide the clinical basis for the study of integration of Traditional Medicin and Western Medicin..
Method
139 acute coronary syndrome patients,who were confirmed by coronary angiography(CAG) were enrolled;Collecting the patients' general information,including symptoms,signs,tongue, pulse,and other clinical informations,then all the patients were divided into four clinical types of TCM syndrome:the heart blood stasis obstruction syndrome group,phlegm turbidity congestion syndrome group,yin-defiency of heart and kidney,yang-qi defiency;We may devided patients into three groups based on severity of coronary artery stenosis after CAG:single-vessel lesion group,double-vessel lesion group,three-vessel lesion group.30 healthy voluteers were enrolled as normal control group;The general information related parameters were collected such as:electrocardiogram,cardiac color Doppler ultrasound,myocardial enzymes,and other indicators.The serum PAI-1、ACE2 of inpatients and the health assessed enzyme linked immunosorbentassay(ELISA).Dates were presented as mean±SD.The significance of the differences among the groups was determined by the T-test and One way analysis of variance;. Linear regression analysis was used to evaluate the relationship between the variables.
Results:
1.We found that high-density lipoprotein(HDL-C) in Coronary heart disease group was lower than the control group;The other indicators such as body mass index(BMI),total cholesterol (TC),triglyceride(TG),low-density lipoprotein(LDL-C),PAI-1 and ACE2 were higher than that of the normal control group;What's more,TC,TG,ACE2 have significant difference between two groups(p＜0.05);
2..Serum concentrations of PAI-1、ACE2 and LDL-C、TG in three vessels disease group were higher than those in one vessels diseaseand two vessels disease groups(p＞0.05);Age and coronary score in three vessels disease were higher than those in other two groups(p＜0.05)
3..ACE2 and the coronary score were positively correlated;but PAI-1 didn't;age and coronary score were positively correlated;
4.PAI-1,ACE2 and the severity of coronary artery disease havn't differences in different gender;
5 TC,TG,ACE2 of the four TCM Syndrome were higher than that of normal control group,but there havn't differences among four groups;
Conclusion:
1.The serum level of PAI-1,ACE2 in Coronary heart disease group was significantly higher than the normal control group,
2.The serum PAI-1 was affected by many factors,so in chlincal it should be considered comprehensivly;
3.Serum ACE2 can be used as one of the risk factors and detection target of the incidence of ACS;
4.PAI-1 has no significant correlation with severity of coronary artery stenosis except ACE2;
5.TCM Syndrome should not assess the severity of coronary artery disease;
6.PAI-1,ACE2 should not be clicinal basis of TCM Syndrome,which had no significant differences among every TCM Syndrome group.PAI-1、ACE2 has no significant differences among TCM Syndrome group.It can't Provides basis for the modern TCM Syndrome.
目的:
通过检测血清纤溶酶原激活物抑制剂-1(PAI-1)、ACE2水平,探讨血清PAI-1、ACE2水平与冠心病中医辨证分型、冠心病病变程度之间的相关性,为冠心病中西医结合的研究提供临床依据。
方法:
临床确诊并经过冠状动脉造影术(CAG)证实的急性冠脉综合征患者139例,正常对照组30例。急性冠脉综合征患者入院时收集一般资料、症状、体征、舌象、脉象等临床资料,进行辨证分型,其中心血瘀阻31例;痰阻心脉47例,;心肾阴虚33例;阳气虚衰28例。根据CAG结果进行病变范围分组,分为单支病变组、双支病变组、多支病变组。正常对照组30例。收集所有研究对象的一般资料,并收集患者入院相关检查指标如:心电图、心脏彩超、心肌酶谱等,患者术前留取空腹血4ml,所有标本在室温下静置1-2小时待血清析出,然后用离心机离心20min(3000r/min),将上清转移至Ependorf管,放置在-70℃冰箱保存,最后统一用酶联免疫吸附法(ELISA)法检测血清PAI-1、ACE2水平。统计采用方差分析、t或t'检验进行冠心病组与正常对照组、各中医辨证分型组、各病变范围组各检测指标的两两比较或直线相关分析。
结果:
1.冠心病组与正常对照组一般资料分析发现,冠心病组除高密度脂蛋白低于正常对照组外,其余指标如体重指数(BMI)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、PAI-1及ACE2水平均高于正常对照组,其中,TC、TG、ACE2有统计学差异(p＜0.05);
2.三支病变组的血清PAI-1、ACE2水平以及年龄、LDL-C、TG、冠脉积分高于单支病变和双支病变组,但只有年龄、冠脉积分有统计学差异;
3.ACE2与冠脉积分呈正相关;PAI-1未发现其相关性;年龄与冠脉积分呈正相关;
4.在不同性别之间,未发现PAI-1、ACE2及冠脉病变严重程度之间有差异;
5.各中医辨证分型与正常对照组之间相比,TC、TG、ACE2水平高正常对照组,有统计学差异,但各证型间无发现统计学差异;
结论:
1.冠心病组血清PAI-1、ACE2水平显著高于正常对照组,具有一定的临床意义;
2.血清PAI-1水平受多种因素影响,临床上需综合考虑;
3.血清ACE2水平可作为ACS的发病危险因素及检测指标之一;
4.血清PAI-1水平与冠脉病变严重程度无明显相关性,ACE2水平与冠脉严重程度的相关性需进一步观察;
5.中医辨证分型不能评估冠脉病变的严重程度;
6.中医辨证分型各组之间,血清PAI-1、ACE2水平无显著差异,不能为冠心病中医现代化辨证分型提供依据。
With the development of economy,there is a gradual increase in the incidence of coronary heart disease,plasminogen activator inhibitor -1(PAI-1) is the main physiological inhibitor of tissue-specific plasminogen activator(t-PA) and urokinase -type plasminogen plasminogen activator(u-PA),PAI-1 plays an important role in the occurrence and development of thrombosis;ACE2 is a new member of the renin - angiotensin system(RAS),it makes the traditional system of RAS more complex.What's more,the study have proved that ACE2 is closely related with coronary heart disease.With the improvement of detection technology,the traditional Chinese medicine diagnosis methods need to be improved and injected new technology and vitality.
Objective:
Through testing the serum fibrinolytic enzyme activator inhibitors - 1(PAI-1),ACE2,we may explore the correlation among the level of PAI-1 and ACE2,TCM syndrome of coronary heart disease and the severity of coronary artery,then provide the clinical basis for the study of integration of Traditional Medicin and Western Medicin..
Method
139 acute coronary syndrome patients,who were confirmed by coronary angiography(CAG) were enrolled;Collecting the patients' general information,including symptoms,signs,tongue, pulse,and other clinical informations,then all the patients were divided into four clinical types of TCM syndrome:the heart blood stasis obstruction syndrome group,phlegm turbidity congestion syndrome group,yin-defiency of heart and kidney,yang-qi defiency;We may devided patients into three groups based on severity of coronary artery stenosis after CAG:single-vessel lesion group,double-vessel lesion group,three-vessel lesion group.30 healthy voluteers were enrolled as normal control group;The general information related parameters were collected such as:electrocardiogram,cardiac color Doppler ultrasound,myocardial enzymes,and other indicators.The serum PAI-1、ACE2 of inpatients and the health assessed enzyme linked immunosorbentassay(ELISA).Dates were presented as mean±SD.The significance of the differences among the groups was determined by the T-test and One way analysis of variance;. Linear regression analysis was used to evaluate the relationship between the variables.
Results:
1.We found that high-density lipoprotein(HDL-C) in Coronary heart disease group was lower than the control group;The other indicators such as body mass index(BMI),total cholesterol (TC),triglyceride(TG),low-density lipoprotein(LDL-C),PAI-1 and ACE2 were higher than that of the normal control group;What's more,TC,TG,ACE2 have significant difference between two groups(p＜0.05);
2..Serum concentrations of PAI-1、ACE2 and LDL-C、TG in three vessels disease group were higher than those in one vessels diseaseand two vessels disease groups(p＞0.05);Age and coronary score in three vessels disease were higher than those in other two groups(p＜0.05)
3..ACE2 and the coronary score were positively correlated;but PAI-1 didn't;age and coronary score were positively correlated;
4.PAI-1,ACE2 and the severity of coronary artery disease havn't differences in different gender;
5 TC,TG,ACE2 of the four TCM Syndrome were higher than that of normal control group,but there havn't differences among four groups;
Conclusion:
1.The serum level of PAI-1,ACE2 in Coronary heart disease group was significantly higher than the normal control group,
2.The serum PAI-1 was affected by many factors,so in chlincal it should be considered comprehensivly;
3.Serum ACE2 can be used as one of the risk factors and detection target of the incidence of ACS;
4.PAI-1 has no significant correlation with severity of coronary artery stenosis except ACE2;
5.TCM Syndrome should not assess the severity of coronary artery disease;
6.PAI-1,ACE2 should not be clicinal basis of TCM Syndrome,which had no significant differences among every TCM Syndrome group.PAI-1、ACE2 has no significant differences among TCM Syndrome group.It can't Provides basis for the modern TCM Syndrome.
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[53]Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.Report of the expert committee on the diagnosis and classification of diabetes mellitus[J].Diabetes Care,2003,26:S5-20.
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[6].Zisman LS ACE and ACE2:a tale of two enzymes Eur Heart J 2005,26(4) 322-324
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[1]Donoghue M,Hsieh F,Baronas E,etal.A novel angiotensin-converting enzyme 2 related carboxypeptidase (ACE2) converts angiotensin I to angiotension(1-9)[J].CircRes,2000,87(5):E1-E9.
[2]Tipnis SR,Hooper NM,HydeR,etal.A Human homolog of angiotensin 2 converting enzyme.Cloning and functional expression asacaptopril 2 in sensitive carboxy peptidase[J].JBiolChem,2000,275(43):33238-33243.
[3]Manfred Boehm M.D,Eliizabeth G,Nabel M.D.Angiotensin Converting Enzyme 2- A New Cardiac REGULATOR[J].N Engl J Med,2002:1.
[4]Carackower M A,Sarao R,Oudit G Y,et al.Angiotensin- converting enzyme 2 is an essential regulator of heart function[J].Nature,2002,417(6891):822-828
[5].Harmer D,Gilberb M,Borman R,et al.Quantitative mRNA expression profiling of ACE2.a novel homologue of angiotensin converting enzyme.FEBS Lett,2002,532(1-2):107-110
[6].Zisman LS ACE and ACE2:a tale of two enzymes Eur Heart J 2005,26(4) 322-324
[7]..Masanobu Y;Yoriko Y;Chengwen Sun;et al Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Causes Long-Term Decrease in Blood Pressure in the Spontaneously Hypertensive Rats[J]Hypertension.2007;49:926.
[8]Vickers C,Hales P,Kaushik V,et al.Hydrolysis of Biologi.Hydrolysis of Biological peptides by Human Angiotensin converting Enzyme-related Carboxy peptidese.[J]Biol Chem,2002,277(17):14838-14843
[9]Rice G I,Thomas DA,Grant PJ,et al.Evaluation of angiotensin-con-verting enzyme(ACE),its homologue ACE2 and neprilysin in angiotensin peptide metabolism.Biochem[J]2004,383:45-51
[10]Zisman LS.ACE and ACE2:a tale of two enzymes.EurHeart[J],2005,26(4):322-324
[11]Tikellis C,Cooper ME,Bialkowski K..Developmental expression of ACE2 in the SHR kidney.A role in hypertension kidney int 2006,70 34-41.
[12]Susan B.GAlicia Allred,Thu H.Le,et al.Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice J Clin Invest.2006 August 1;116(8):2218-2225.
[13]FionaJ.Warner,RebeccaA.Le w,A.I an Smith,Daniel W.Lambert,Nigel M.Hooper,and Anthony J.Turner:Angiotensin Converting Enzyme 2(ACE2),but not ACE,Is Preferntially Localized to the Apical Surface of Polarized Kidey Cells.[J]THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL.280,NO.47pp.39353-39362
[14]Loot AE Roks AJ,Henning R H,et al.Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats[J]Circulation,2002,105(13):1548-1550
[15]王江、田颖、聂凌等心力衰竭患者心肌组织ACE2表达与心功能的关系[J]局解手术学杂志2007,16(1)13-15
[16]Zisman LS,Keller RS,Weaver B,et al.Increased angiotensin(1-7)-forrning activity in failing human heart ventricles.Evidence for upregulation of the angiotensin- Enzyme homologue ACE2[J].circulation,2003, 108(14) : 1707-1712.3, November 25, 2005
[17] Koichi Yamamoto, Mitsuru Ohishi, Sumio Sugano, et al l. Deletion of Angiotensin Converting Enzyme 2 Accelerates pressure Overload-Induced Cardiac Dysfunction by increasing Local Angiotensin II. Hypertension 2006; 47; 718-726
[18] Donoghue M, Wakimoto H , Maguire CT, et al. Heartblock, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins .J MOL cell cardioal, 2003, 35 (9): 1043-1053