【作者】 李郁；

【导师】 罗兴林；

【作者基本信息】 泸州医学院 ， 内科学， 2009， 硕士

【摘要】 目的:探讨转化生长因子-α(TGF-α)、核因子-κB(NF-κB)在老年高血压患者及老年高血压合并冠心病患者颈动脉、肱动脉重构以及心脏重构中的意义。方法:1.于清晨采集实验组和对照组空腹外周血清,采用放免法测定37例老年高血压患者、34例老年高血压合并冠心病患者及16例正常对照组血清中TGF-α的浓度。2.提取实验组和对照组清晨空腹外周血单个核细胞,制作细胞涂片,用免疫组化方法检测其中核因子NF-κB活化表达率。3.用血管超声检测颈动脉血管内膜-中层厚度(CCAIMT)、颈动脉内径、颈动脉血流速度以及颈动脉粥样斑块形成情况,根据Crouse法计算颈动脉斑块积分,并检测肱动脉内径以及内膜-中层厚度(GdmIMT);经胸超声心动图检查,检测病例组及对照组室间隔厚度(IVST)、左室后壁舒张末期厚度(LVPWT)、左室舒张末期内径(LVDd)、左室最大长轴缩短率(FS),Simpson法测量射血分数(EF),频谱多普勒测量二尖瓣舒张早期峰值速度MVe、房缩期峰值速度MVa。根据Devereux等公式计算左室心肌重量(LVM=1.04×[(IVST+LVPWT+LVDd)3-LVDd 3]-13.6)、左室质量指数(LVMI =LVM/BSA,体表面积(BSA)= 0.006×身长(cm)+0.013×体重(kg))等超声指标。4.统计分析:所有数据均采用均数±标准差表示,应用SPSS13.0统计软件进行统计学处理。统计方法组间对照采用t检验及方差分析,不同指标间作线性相关分析,以P<0.05认为具有显著性差异。结果:TGF-α、NF-κB水平高血压合并冠心病组明显高于高血压组,高血压组显著高于正常对照组。血清TGF-α水平与外周血单个核细胞NF-κB活化率呈显著正相关(r=0.678,P<0.01),直线回归方程为y=10.28+0.848x。TGF-α、NF-κB水平与颈动脉、肱动脉的内径、内膜-中层厚度、血管壁/腔比值、颈动脉斑块积分、颈动脉阻力指数、搏动指数等反映血管重构的指标呈正相关。TGF-α水平与反映心脏重构指标左室舒张末期容积、室间隔、左室后壁厚度、左室质量指数呈正相关;与反映心脏收缩功能指标EF、FS值呈负相关。NF-κB水平与室间隔厚度、左室质量指数呈正相关;与EF值呈负相关。结论:1.高血压、冠状动脉粥样硬化两种疾病互为因果,互相促进,二者的发病机制可能均与血管炎症有关,其病理基础为心血管重构。2.血清TGF-α水平与外周血单个核细胞NF-κB活化率相关,TGF-α可能通过NF-κB参与细胞信号传导。3.TGF-α、NF-κB水平与颈动脉、肱动脉IMT相关;与左室扩大,左室质量指数及左室收缩功能相关,二者均为老年心血管疾病的心血管重构及不良预后的指标。更多还原

【Abstract】 Objective:To investigate the correlation of transforming growth factor-α(TGF-α), nuclear factor-κB (NF-κB) with carotid artery, brachial artery remodeling and of cardiac remodeling in elderly patients with hypertension and elderly hypertensive patients with coronary heart disease. Methods: (1) In the early morning gathering experimental group and the control group fasting circumference blood serum. To measure the serum concentrations of TGF-αby RIA of 37 cases of elderly patients with hypertension, 34 cases of elderly hypertensive patients with coronary heart disease and 16 cases of normal control group. (2) Extracting of experimental group and control group fasting peripheral blood mononuclear cells, and manufacturing cell smears,then using immunohistochemical method to detect the nuclear factorκB activation expression rate.(3) Use vascular ultrasound detects the arteria carotis communis intima-media thickness (CCAIMT),carotid diameter, carotid artery blood flow velocity and carotid artery plaque formation. Compute carotid plaque score according to the Crouse method. Detect brachial artery diameter and the brachial artery intima-media thickness (gdmIMT). Other echocardiography parameters was also detected and recorded, such as diastolic diameter, thickness of the IVS and LV posterior wall, ejection fraction, the ratio of left ventricular fractional shortening (FS), the mitral early and late diastolic flow velocity MVe, MVa. Calculate the left ventricular mass (LVM) according to Devereux formula (LVM=1.04×[(IVST+LVPWT+VDd)3-LVEDd3] -13.6), left ventricular mass index [LVMI=LVM/BSA, body surface area (BSA) =0.006×body length(cm)+0.013×weight (kg)]. Results: The TGF-α, NF-κB level of patient with hypertension and coronary heart disease was significantly higher than the hypertension group, and the level of hypertension group was significantly higher than the normal control group. TGF-αserum level and peripheral blood mononuclear cell NF-κB activation rate were significantly positively correlated (r=0.678,P<0.01), linear regression equation was y=10.28+0.848x. There was a positive correlation among TGF-α, NF-κB levels and vascular remodeling indicators, which can reflect by carotid artery, brachial artery diameter, intima-media thickness and vascular wall/cavity ratio,carotid artery plaque score, carotid artery resistance index and pulsatility index.TGF-αlevel is positively correlated with left ventricular diastolic diameter, thickness of the IVS, LV posterior wall and LVMI, those are indicators of cardiac remodeling. And TGF-αlevel also negatively correlated with EF, FS, which reflect the cardiac systolic function. NF-κB level and ventricular septal thickness, left ventricular mass index are positively correlated. The relationship between NF-κB level and EF values are negative correlation. Conclusion: (1) Hypertension and coronary atherosclerosis two diseases are both cause and effect relation, promote mutually. Both of them are related to the pathogenesis of vascular inflammation, and those pathological bases for cardiovascular remodeling. (2) Blood serum TGF-αlevel and peripheral blood monocyte NF-κB activation rate related. TGF-αpossibly through NF-κB participates in the cell signal transduction. (3) TGF-α, NF-κB serum levels and carotid artery, brachial artery IMT related; and they also related with left ventricular enlargement, left ventricular mass index and left ventricular systolic function. Both TGF-αand NF-κB are cardiovascular remodeling index of elderly cardiovascular disease and poor prognosis indicators.更多还原