血管紧张素转换酶基因与缺血性脑卒中发病的关系

Relationship between angiotensin converting enzyme gene and ischemic stroke

目的探讨血管紧张素转换酶（ACE）基因与缺血性脑卒中（IS）发病的关系。方法1应用聚合酶链反应（PCR）和变性高效液相色谱技术筛查了454例IS患者（病例组）和334例非IS患者（对照组）ACE基因I/D多态性的分布,详细记录卒中危险因素。2选择40只SD大鼠制备低氧-窒息模型和单纯窒息模型,同时选择29只易卒中型自发性高血压大鼠（SHR-SP）。检测血浆血管紧张素（Ang）水平的变化。结果病例组的DD、ID、Ⅱ型的频率分别为22.5%、43.4%和34.1%,对照组为17.4%、45.5%和37.1%,ACE基因DD型与大动脉粥样硬化型IS相关。SHR-SP血浆Ang水平〔（164.49±34.58）ng/L〕较正常SD大鼠〔（150.92±24.92）ng/L〕高,但差异无显著性（P〉0.05）;窒息组和低氧-窒息组血浆Ang水平分别为（382.84±62.75）ng/L和（295.90±55.07）ng/L,均显著高于正常SD大鼠水平（P均〈0.01）。吸烟、酗酒群体内病例组以及伴糖尿病群体的DD型和D等位基因的相对风险率均高于相应对照组,而Ⅱ型和Ⅰ等位基因的相对风险率均低于相应对照组。结论DD基因型是IS的易患因子;Ang参与了低氧应激过程;ACE基因与吸烟、酗酒、糖尿病在IS的发病过程中存在协同作用。

Objective To study relationship between angiotensin converting enzyme （ACE） gene and ischemic stroke （IS）. Methods （1）Four hundred and fifty-four patients and 334 controls were recruited in our study, their I/D polymorphisms of ACE gene were detected by polymerase chain reaction （PCR） and denaturing high performance liquid chromatogram, and their risk factors of IS were recorded at the same time. （2）In addition, 29 stroke- prone spontaneously hypertensive rats （SHR- SP） and 40 Sprague -Dawley （SD） rats were enrolled, and hypoxia - apnoea animal models and simple apnoea animal models were used at the same time. Their plasma angiotensin n （Ang n ） levels were determined. Results The frequencies of DD, ID and II genotype in IS patients were 22.5%, 43. 4%and 34.1%, respectively, and 17.4%, 45.5% and 37.1%, respectively in controls. DD genotype was associated with large artery arterioslarosis （LAA）. Plasma Ang n level in SHR -SP group was （164.49±34. 58） ng/L, and it was higher than that in control group [（150. 92 ± 24. 92） ng/L] with no significant difference （P〉0.05）. Ang n levels in apnoea and hypoxia -apnoea group were （382.84± 62.75） ng/L and （295.90± 55.07） ng/L, respectively, and they were significantly higher than that in control group （all P〈0.01）. The relative risks of DD genotype and D alleles in IS patients with smoking, alcohol abuse, or with diabetes mellitus were higher than those in controls, but Ⅱ genotype and Ⅰ alleles were lower than those in controls. Conclusion DD genotype is a risk factor for IS, Ang n takes part in the course of hypoxia - stress, and it is correlated with smoking, alcoh＇ol abuse and diabetes mellitus in the pathogenesis of IS.