高同型半胱氨酸血症对急性ST段抬高型心肌梗死患者淋巴细胞KV1.3-CaN-NFAT信号通路的影响  

Influence of hyperhomocysteinemia on signal pathway of KV1.3-CaN-NFAT in lymphocytes of patients with acute ST-segment elevation myocardial infarction

作　　者：王玉岭[1] 贾绍斌[2] 侯建军[2] 丛广志[2] 杨绍兵[1] 崔莹[1] 王凯[1] 

机构地区：[1]宁夏医科大学,宁夏银川750004 [2]宁夏医科大学总院心脏中心,宁夏银川750004

出　　处：《西安交通大学学报（医学版）》2016年第3期412-417,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：宁夏医科大学优势学科群建设科研项目(No.xy2014016)~~

摘　　要：目的观察不同水平高同型半胱氨酸血症(Hhcy)对急性ST段抬高型心肌梗死(STEMI)患者淋巴细胞内电压门控性钾离子通道(KV1.3通道)-钙调神经磷酸酶(CaN)-活化T细胞核因子(NFAT)-炎性因子(IL-6、TNF-α)mRNA及蛋白表达水平的影响。方法入选STEMI患者90例,根据血浆Hcy水平分为3组:实验A组(STEMI组,Hcy<15μmol/L,n=30)、实验B组(STEMI+轻度Hhcy组,Hcy 15~30μmol/L,n=30)、实验C组(STEMI+中度Hhcy组,Hcy>30μmol/L,n=30),另选取健康体检者30例为对照组。抽取血标本后使用全自动生化仪测定血浆Hcy浓度,密度梯度离心法提取淋巴细胞,RT-PCR检测KV1.3、CnAα、NFAT1、IL-6、TNF-αmRNA的表达,Western blot检测KV1.3、CnAα、NFAT1蛋白的表达。结果各实验组较对照组KV1.3、CnAα和NFAT1的mRNA和蛋白表达水平升高(P<0.05或P<0.01),各实验组间两两比较显示,实验B组较实验A组表达水平升高(P<0.05或P<0.01),实验C组较实验B组和实验A组表达水平升高(P<0.05或P<0.01)。各实验组IL-6和TNF-α的mRNA表达水平高于对照组(P<0.01),各实验组间两两比较显示,实验B组较实验A组表达水平升高(P<0.01),实验C组较实验B组和实验A组表达水平升高(P<0.01)。实验组血浆Hcy水平与KV1.3mRNA和蛋白表达之间呈正相关,相关系数分别为r=0.503(P=0.000)、r=0.726(P=0.000)。结论血浆Hcy浓度水平越高,STEMI患者淋巴细胞内KV1.3-CnAα-NFAT1的mRNA和蛋白表达水平及炎性因子IL-6、TNF-α的mRNA表达水平越高,这一信号通路可能是Hcy加重STEMI炎症反应的机制之一。Objective To observe the influence of different level of hyperhomocysteinemia on mRNA and protein expressions of KV1. 3, CaN, NFAT, IL-6 and TNF-α in lymphocytes of patients with acute ST-segment elevation myocardial infarction （STEMI）. Methods We selected 90 STEMI patients and divided them into three groups according to the level of plasma homocysteine., the first experimental group （STEMI group, Hcy〈15 μmol/L, n ：30）, the second experimental group （STEMI with mild Hhcy group, Hcy 15~30 μmol/L, n =30） and the third experimental group （STEMI with intermediate Hhcy group, Hcy〉30 μmol/L, n = 30）. Another 30 healthy examined people were selected as control group （n = 30）. Peripheral lymphoeytes were isolated by Ficoll density gradient centrifugation. The Hcy in the plasma was measured with the IMX assays. Real-time quantitative PCR （RT-PCR） was used to detect mRNA expressions of KV1.3, CnAa, NFAT1, IL-6 and TNF-α and Western blot technique was used to detect the expressions of KV1.3, CnAa and NFAT1. Results The mRNA and protein expression levels of KV1.3, CnAa and NFAT1 in each experimental group were significantly higher than those in control group （P〈0.05 or P〈0.01）. Multiple comparison in each experimental group showed that compared with that in the first experimental group, the expression level of the second experimental group increased （P〈0.05 or P〈0.01） and compared with first and second experimental groups, the expression level of the third experimental group increased （P^0.05 or P〈0.01）. The mRNA expression levels of IL-6 and TNF-α in each experimental group were significantly higher than those in control group （ P 〈 0. 05 or P 〈0. 01 ）. Multiple comparison in each experimental group showed that compared with that in the first experimental group, the expression level of the second experimental group increased （P〈0.05 or P〈0.01）and compared with first and second experimental groups, the expression level of the third experimental group i

关 键 词：高同型半胱氨酸血症 急性ST段抬高型心肌梗死 淋巴细胞 信号通路 炎症反应 白细胞介素-6(IL-6) 肿瘤坏死因子-α(TNF-α) 

分 类 号：R543.3[医药卫生—心血管疾病]