血浆组织蛋白酶和炎症因子含量与腹主动脉瘤危险度关系的研究

发布时间：2018-05-02 18:56

本文选题：组织蛋白酶L + 组织蛋白酶K　；参考：《华中科技大学》2016年博士论文

【摘要】：第一部分血浆组织蛋白酶L、K和V含量与腹主动脉瘤危险度关系目的组织蛋白酶L (CatL)、组织蛋白酶K (CatK)以及组织蛋白酶V (CatV)作为潜在的弹性蛋白酶参与人动脉壁重塑。本文的目的是观测在腹主动脉瘤(AAA)患者的血浆中这些组织蛋白酶是否发生改变。方法476名男性AAA患者作为实验组,200名年龄匹配的男性作为对照组。取血浆并用ELISA检测CatL、CatK和CatV的浓度。t检验、ROC曲线明确实验组和对照组之间是否存在差异。皮尔森相关分析检验CatL与AAA疾病相关危险因素之间的关系。逻辑回归分析验证血清学指标是否能作为疾病的独立预测指标。结果t检验发现AAA病人血浆中CatL的含量高于对照组人群(p0.0001),而CatK和CatV含量在AAA病人中降低(P=0.052, P=0.025). ROC曲线分析再次证实了CatL的含量在AAA病人血浆中表达增高具有统计学意义(p0.001)。在潜在的混杂性因素中,吸烟、血管紧张素转化酶(ACE)抑制剂、阿司匹林、氯吡格雷和他汀的使用与血浆CatL含量密切相关。皮尔森相关分析指出血浆CatL与组织蛋白酶S (CatS)(r=0.43,P0.0001)、体重指数(BMI)(r=0.07,P=0.047)以及最大动脉直径(r=0.29,P0.001)呈正比例增加；而与最低踩臂指数(ABI)呈负相关(r=0.22,p0.001)。用偏相关分析对上述可能的混杂因素进行校正后,血浆CatL与CatS (r=0.43,P0.0001)、最大动脉直径(r=0.212,P0.001)仍具有正相关,与最低ABI呈负相关(r=0.10,P=0.011)。多元逻辑回归分析提示在对上述相同的混杂因素进行校正前后(优势比(OR)分别为OR=3.04, P0.001、OR=2.42, p0.001)均提示血浆CatL为AAA的危险因子。结论血浆中CatL的含量与动脉直径大小、最低踝臂指数(ABI)的相关性提示这种半胱氨酸蛋白酶在人外周动脉疾病和AAA中发挥重要作用。第二部分血浆炎症因子含量与腹主动脉瘤危险度关系目的AAA斑块中有大量的炎症细胞浸润,以分泌炎性因子并促进动脉瘤进展为特征。本文的目的是检测外周血细胞因子的含量是否能够预测AAA的危险程度。方法476名男性AAA患者作为实验组,200名年龄匹配的男性作为对照组。取血浆并用ELISA检测白介素6(IL-6)、白介素10(IL-10)、白介素17A (IL-17A)、Y干扰素(IFN-Y)和C反应蛋白(CRP)的浓度。结果AAA病人血浆中IL-6、IFN-γ、IL-10和IL-17A含量较对照组低,而CRP含量高于对照组。IL-10的浓度与IFN-γ、IL-17A、IL-6呈正比,但与CRP无关;此外,IL-10的浓度与收缩压呈负相关,而CRP与舒张压、体重指数(BMI)呈正比。CRP是AAA的独立危险因子并与动脉直径呈正相关。IFN-γ、IL-17A和CRP与AAA横截面积呈正相关。IL-10与AAA生长速率呈正相关。AAA病人外周血CRP高于均数时动脉瘤死亡的危险性会增加。结论AAA病人中IFN-γ、IL-10、IL-17A含量减少,IFN-γ和IL-17A与AAA横截面积呈正相关,IL-10与AAA生长速率、IFN-γ、IL-17A呈正相关,提示Th1、Th2和Th17细胞免疫反应参与了人AAA发病机制。
[Abstract]:Part I relationship between plasma cathepsin K and V levels and risk of abdominal aortic aneurysm objective cathepsin L, cathepsin K (Catk) and cathepsin V (Catv) are potential participants in arterial wall remodeling. The aim of this study was to observe the changes of these cathepsin in plasma of patients with abdominal aortic aneurysm (AAA). Methods 476 male patients with AAA were used as control group of 200 age matched males in the experimental group. The plasma levels of CatLK and CatV were measured by ELISA. T test was used to determine whether there was a difference between the experimental group and the control group. Pearson correlation analysis examined the relationship between CatL and risk factors associated with AAA disease. The logistic regression analysis verifies whether the serological index can be used as an independent predictor of disease. Results t test showed that the content of CatL in plasma of AAA patients was higher than that of control group (P 0.0001), while the contents of CatK and CatV in AAA patients were decreased by 0.052 and 0.025% respectively. ROC curve analysis confirmed that the increase of CatL expression in plasma of AAA patients was statistically significant (P 0.001). Among the potential confounding factors smoking angiotensin-converting enzyme (ACE) inhibitors aspirin clopidogrel and statins were associated with plasma CatL levels. Pearson correlation analysis showed that plasma CatL was increased in proportion to cathepsin S (cat) 0.43 (P 0.0001), body mass index (BMI) 0.07 ~ (0. 047) and maximum arterial diameter (r ~ (0.29) P ~ (0.001), but negatively correlated with minimum arm index (n = 0.22), P ~ (0.001). After correction of the above possible confounding factors by partial correlation analysis, the plasma CatL was positively correlated with CatS 0.43 (P 0.0001), and the largest artery diameter was 0.212g / P 0.001), and negatively correlated with the lowest ABI, and negatively correlated with the lowest ABI. Multiple logistic regression analysis showed that plasma CatL was a risk factor for AAA before and after correction (odds ratio: OR3.04, P0.001OR2.42, p0.001). Conclusion the correlation between plasma CatL content and arterial diameter and minimum malleolus brachial index (ABI) suggests that cysteine protease plays an important role in human peripheral artery disease and AAA. The relationship between plasma inflammatory factor content and risk of abdominal aortic aneurysm objective A large number of inflammatory cells infiltrate in AAA plaque characterized by secretion of inflammatory factors and promotion of aneurysm progression. The aim of this study was to determine whether the level of cytokines in peripheral blood could predict the risk of AAA. Methods 476 male patients with AAA were used as control group of 200 age matched males in the experimental group. The concentrations of interleukin 6 (IL 6), interleukin 10 (IL 10), Interleukin-17A (IL 17 A), interferon Y (IFN-Y) and C reactive protein (CRP) were determined by ELISA. Results the levels of IL-10 and IL-17A in plasma of patients with AAA were lower than those of the control group, while the concentration of CRP was higher than that of the control group. The concentration of IL-10 was directly proportional to the concentration of IL-17A4 IL-6, but not related to CRP. In addition, the concentration of IL-10 was negatively correlated with systolic blood pressure, while that of CRP was negatively correlated with diastolic blood pressure. BMI-CRP was an independent risk factor for AAA and positively correlated with arterial diameter. IL-17A and CRP were positively correlated with AAA cross-sectional area. IL-10 was positively correlated with AAA growth rate. The risk of aneurysm death was increased when CRP in peripheral blood was higher than the mean in patients with AAA. Conclusion there is a positive correlation between IL-10 and AAA cross sectional area in patients with AAA. There is a positive correlation between IL-10 and AAA growth rate and IL-17A, which suggests that Th1Th _ 2 and Th17 cell immune reaction may play an important role in the pathogenesis of human AAA.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R543.16

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