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心血管危险因素和侯选基因多态性对动脉顺应性影响的研究

The Effect of Cardiovascular Risk Factors and Polymorphism of Candidate Genes on Vascular Compliance

【作者】 蒋素华

【导师】 李新立;

【作者基本信息】 南京医科大学 , 内科学, 2004, 硕士

【摘要】 第一部分 心血管危险因素与小动脉弹性的相关性研究 目的 通过病例对照研究,了解影响小动脉弹性的主要心血管危险因素及多种危险因素同时存在时对小动脉影响的相加协同作用。 方法 (1)采用CVProfilor DO-2020动脉脉搏分析仪对232例符合入选条件的受试者测量大、小动脉弹性指数(C1、C2),并根据小动脉弹性指数结果把受试者分为C2异常组(119例)和对照组(113例)。(2)同时采集病史、查体及进行有关血生化指标检查。(3)根据心血管危险因素数目对受试者进行亚组分析。 结果 (1)C2异常组年龄、总胆固醇、低密度脂蛋白-胆固醇、血糖、收缩压和舒张压明显高于对照组,而C2明显低于对照组。(2)单因相关分析,年龄、总胆固醇、低密度脂蛋白-胆固醇、血糖、收缩压和舒张压与C2呈负相关。(3)按主要危险因素个数所分亚组的C2(ml/mmHg×100)分别为6.5±2.6(0亚组)、5.4±2.3(1亚组)、4.7±2.7(2亚组)、3.1±1.6(3亚组),各亚组间除1和2亚组之间(P=0.073)外均有显著性差异(P<0.05)。(4)C2水平与主要危险个数呈负相关(r=-0.409,P<0.001)。 结论 (1)年龄、总胆固醇、低密度脂蛋白-胆固醇、血糖、收缩压和舒张压水平是影响小动脉弹性的主要心血管危险因素;它们对小动脉弹性影响是连续的。(2)多种危险因素并存时,通过相加协同作用使小动脉弹性明显减退。 第二部分 α—内收蛋白基因多态性与小动脉弹性的关系研究 目的 探讨α-内收蛋白基因Gly460Trp多态性与小动脉弹性的相关性。 南京医科大学硕士学位论文方法(z)采用CvPfofilor DO一2020动脉脉搏分析仪测量小动脉弹性指数CZ。(2)用突变分离聚合酶链反应(MS一PCR)一琼脂糖凝胶电泳检测基因型。结果(1) CZ异常组Trp/Trp基因型频率、Trp等位基因频率显著高于对照组(33.6%与14.8%,P<0.01;56.0%与46.0%,P<0.05)。(2)Trp/Trp基因型与其它基因型比较CZ、SBP、DBP差异有显著性(P<0.肠)。(3)通过LogistiC回归排除10种环境危险因素影响后,Trp/Trp基因型仍是CZ异常的危险因素(P一0.娜2,OR月.3,Cl1 .1一5.0)o结论a一内收蛋白基因Gly460Trp多态性与小动脉弹性有显著的相关,Trp/Trp基因型是小动脉弹性异常的敏感基因型。第三部分降压治疗对颈动脉内膜中层厚度和动脉顺应性影晌的研 究目的探讨降压治疗对颈动脉内膜中层厚度(IMT)和动脉顺应性影响的关系及其临床意义。方法分别选取正常对照组45例、高血压控制组35例和高血压未控制组36例,使用美国产HD工一2 020动脉测试仪同步记录血压和动脉顺应性(大动脉弹性Cl,小动脉弹性C2),美国产HP5500超声多普勒高分辫率7.SMHz扫描探头测量颈动脉工MT和血管内径变化。结果高血压未控制组颈动脉IMT明显增厚,与高血压控制组和正常对照组比较有显著性差异(P<0.肠),后二组间无统计学意义(p>.05)。颈动脉内径:高血压未控制组与对照组间有差异(p<0.01),高血压未控制组与控制组间无差异(P>.05),三组间收缩压(SBP)、舒张压(DBP)和脉压(PP)比较均有差异(P<0.01),高血压未控制组C1和CZ均低于对照组和高血压控制组(p<0.01),后二组间无差异(P>.05)。Cl:三组均与SBP和pP呈负相关(r一 0.324,p<0 .05;r=一0.482,P<0.01:f=一0.342,P<0.05;r=一0.384,P<0.05; 南京医科大学硕士学位论文r二一0.315,p<0.05;r一0.365,p<0.05)。Cl只与对照组颈动脉IMT呈负相关(r一0.369,p<0.01);C2与对照组和高血压控制组的颈动脉IMT呈负相关(r一0.451,p<0.01;r一0.462,p<0.01)。高血压控制组和未控制组CZ与SBP和PP呈负相关(r=一0.440,p<0.肠;r=一0 .4 41,p<0.05;r=一0.372,p<0.05;r=一0.413,P<0.05),三个组的CZ与DBP均无相关·}生。结论降压治疗可逆转或延缓颈动脉IMT的进程,动脉顺应性与SBP、PP相关性优于颈动脉IMT。

【Abstract】 1 Association of cardiovascular risk factors and small arterial elasticityObjectives Based on case-control study, we explore what are major cardiovascular risk factors affecting small arterial elasticity and if small arterial elasticity decreases significantly in patients with multiple risk factors.Methods (1) 232 eligible subjects were recruited in this study. Arterial elastic indexes ( Cl-large artery and C2-small artery) were measured with CVProfilor DO-2020 artery pulse contour analysis instrument. Abnormal C2 group (n=119) and control group (n=11 13) were divided according to the levels of C2. (2) Meanwhile, the medical history, physical exam and biochemistry variables were collected. (3) According to the number of major cardiovascular risk factors, 232 subjects were categorized into four subgroups (0 to 3).Results (1) The levels of age, cholesterol (CHOL), low density lipoprotein- cholesterol (LDL-C), serum glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in abnormal C2 group were significantly higher than that in control group, while the levels of C2 were lower than that in control group. (2) The levels of age, CHOL, LDL-C, serum glucose, SBP and DBP were negatively correlated with C2. (3) The levels of C2(ml/mmHg X 100) were 6.5+ 2.6(subgroup 0),5.4+2.3(subgroup 1),4.7 + 2.7(subgroup 2),3.1 + 1.6(subgroup 3) respectively. The levels of C2 were statistically different between any two subgroups (P<0.05) except between subgroup 1 and subgroup 2(P=0.073). (4) The levels of C2 were negatively correlated with the number of major cardiovascular risk factors (r=-0.409,P<0.001). Conclusions (1) Aging and abnormalities of CHOL, LDL-C, serum glucose, SBP and DBP were major cardiovascular risk factors of small arterial elasticity. Their effects on C2 were continuously linear. (2) Small arterial elasticity in patients with multiple risk factors decreases more significantly than that in patients without apparent risk factors. It is suggested they may have cooperative effects on small arterial elasticity.?2 Association of polymorphism of alpha-adducin gene and small artery elasticityObjectives To investigate the association of the polymorphism of alpha-adducin gene with small artery elasticity.Methods (1) Small artery elasticity index (C2) was measured with CVProfilor DO-2020. (2) Genotypes were determined by mutagenic separated PCR (MS-PCR)-agarose gel electrophoresis. Results (1) The frequencies of Trp/Trp genotype and Trp allele in abnormal C2 group were significantly higher than that in control group (33.6% vs 14.8%,P<0.01;56.0% vs 46.0%,P<0.05). (2) C2. SBP and DBP in Trp/Trp genotype were significantly different from that in Gly/Gly+Gly/Trp genotype (P<0.05). (3) After the influences of ten environmental factors were excluded through logistic regression analysis, Trp/Trp genotype was still the risk factor associated with abnormal C2 (P=0.032, OR=2.3, CI 1.1 -5.0).Conclusions The polymorphism of alpha-adducin gene is associated with small artery elasticity. Trp/Trp is a sensitive genotype reflecting the abnormality of small arterial compliance. 3 The effect of antihypertensive therapy on intima-media thickness of the common carotid artery and vascular complianceObjective To investigate the effect of antihypertensive therapy on intima-media thickness (IMT) of the common carotid artery(CCA) and vascular compliance.Methods 116 subjects were divided into three groups,45 normotensive individuals as the control group,35 subjects in controlled hypertension group, and 36 patients in uncontrolled hypertension group. Blood pressure and artery compliance (Cl-large artery,C2-small artery) were detected using HDI DO-2020. IMT of CCA was measured using HP5500 ultrasound with a high-resolution 7.5MHz scan head. Results IMT of the CCA of EH-uncontrolled group was markedly increased, compared with control group and EH-controlled group (P<0.01), but there was no statistical difference between control and EH-controlled groups(P>0.05).Lumen diameter(LD) of CCA between control and EH-uncon

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