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目的:本研究的目的是确定是否血管紧张素转换酶抑制剂的插入/缺失(I/D),血管紧张素II 1型受体(AT1R),和血管紧张素原(AGT)基因多态性与韩国女性特发性复发性流产(RSA)的相关性。

研究设计:共251例不明原因流产,和126名健康对照者中至少有一个活产无流产史。

、结果:比值比(OR)的ACE ID (OR = 2.423;95%可信区间(CI)= 1.417-4.142; p = 0.001)和ACE II(OR= 2.050;95% CI = 1.143–3.675;P = 0.018)的ACE DD基因型之间差异极显著例特发性RSA与对照组无显著性差异;然而,患者和对照组之间就AT1R 1166a>C 和AGT M235 III类一致T多态性有。

在一个单倍型分析I-A(P = 0.010),D-A (p = 0.004), I-A-T (p = 0.033), D-A-T (p = 0.0005), 和D-C-T (p = 0.013)和协同效应在患者和对照组的方法,导出多态性对具有显著效果。

结论:本研究表明,ACE,AT1R和AGT基因多态性和单倍型为在韩国女性特发性RSA的风险的遗传因素。

The renin–angiotensin–aldosterone system (RAAS) or therenin–angiotensin system (RAS), which is one of the important factors controlling blood pressure, volume in the cardiovascular system, and electrolyte balance is a hormone system.肾素血管紧张素醛固酮系统(RAAS––)或肾素-–血管紧张素系统(RAS),这是一个控制血压的重要因素,在心血管系统的体积,和电解质的平衡是一种激素系统。

Angiotensinogen (AGT), which is produced by the liver, is part of the renin–angiotensin system and is a major target for drugs that lower blood pressure. AGT is also known as a renin . Angiotensin I is produced by the action of rennin on angiotensinogen. Angiotensin I is catalyzed by angiotensin I converting enzyme (ACE), which converts angiotensin I to angiotensin II, a potent vasoconstrictor in the cardiovascular system.血管紧张素原(AGT),它是由肝脏产生的,是肾素血管紧张素系统的一部分,是–降血压药物的主要目标。

AGT也被称为肾素底物。

血管紧张素是由肾素-血管紧张素作用产生的。

血管紧张素1是由血管紧张素1转换酶(ACE),将血管紧张素1转换为血管紧张素II,在心血管系统中一种有效的血管收缩剂。

Moreover, ACE degrades bradykinin, a potent vasodilator, and other vasoactive peptides. Angiotensin II has vasopressor(血管加压素)effects and regulates aldosterone secretion. Angiotensin II functions through at least two types of receptors (angiotensin II type 1 receptor [AT1R] and angiotensin II type 2receptor [AT2R]).此外,ACE降解缓激肽,是一个良好的血管扩张,和其他血管活性肽。

血管紧张素II有升压和调节醛固酮分泌作用。

血管紧张素II至少通过两种类型的受体(血管紧张素II 1型受体[AT1R]和血管紧张素II型受体[AT2R])发挥作用。

AT1R has vasopressor effects and regulates aldosterone secretion. AT1R mediates the major cardiovascular effects, including vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, vascular smooth muscle cell proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium reuptake, modulation of central sympathetic nervous system activity, and cardiac contractility [2].AT1R(血管紧张素II 1型受体)有升高血压和调节醛固酮分泌的作用。

AT1R介导的心血管作用,包括血管收缩,醛固酮的合成与分泌,加压素分泌增加,血管平滑肌细胞增生,肾血流量减少,肾肾素抑制,肾小管对钠的重吸收,中枢交感神经系统活动和心肌收缩能力的调制[ 2 ]。

Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and production of plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2),which are significant components of the fibrinolysis cascade. AT1R and AT2R are expressed in human embryos during pregnancy and are included in organ development.血管紧张素II有形成血栓的潜力,通过血小板粘附和聚集作用,血浆纤溶酶原激活物抑制剂-1(PAI-1)聚合和纤溶酶原激活物抑制物-2(PAI-2)的生产,并且这是纤溶级联的重要组成部分。

AT1R和AT2R的表达在人类胚胎在妊娠过程中,包括在器官发育阶段。

ACE, AT1R, and AGT gene polymorphisms have been reported to be associated with abortion [3–5]. There genes are also related to various vascular diseases, such as hypertension, coronary artery disease, ischemic stroke, cardiovascular disease, and pregnancy-related diseases, such as pregnancy-induced hypertension (pre-eclampsia) or serious pregnancy complications [6,7]. ACE,AT1R,和AGT基因多态性已被报道与堕胎相关[ 3 –5]。

有基因也与多种血管性疾病有关,如高血压、冠状动脉疾病、缺血性中风、心血管疾病,与妊娠有关的疾病,如妊娠高血压综合征(先兆子痫)或严重的妊娠并发症[6,7]。

Based on biological functions, these three genes can be candidates for RSA. Even though there are many studies pertaining to ACE I/D, AT1R1166A>C, and AGT M235T polymorphisms, this is the first report which evaluates these three genes in idiopathic RSA by using haplotype-based analyses. We therefore determined the association between ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in Korean women with idiopathic RSAs.基于这三个基因的生物学功能,可对RSA的候选人。

尽管有许多与ACE I / D,at1r1166a >C,和AGT M235T多态性有关的研究,这是第一次报告的评价这三个基因在原发性RSA 采用单倍型分析。

因此我们确定ACE I / D,AT1R 1166a>C,和AGT M235T基因多态性与韩国女性原发性习惯性流产之间有关联。

2. Materials and methods2。

材料与方法2.1. PatientsThe patient group was comprised of 251 Korean women (age range; 22–45 years, mean age SD:31.97±4.30 years, BMI:21.58±3.58) who were diagnosed with at least three consecutive spontaneous abortions. The patients were enrolled between March 1999 and February 2008 in the Department of Obstetrics and Gynecology, and the Fertility Center of CHA Bundang Medical Center in Seongnam, South Korea. Patients with a pregnancy loss were identified by hCG testing, ultrasound, and/or physical examination (<20 weeks gestational age).患者组由251个韩国女性(年龄范围;22–45岁,平均年龄4.30年,SD;BMI;31.97,21.58 3.58)确诊为至少三个连续自然流产。

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