本文選題：組織蛋白酶L + 組織蛋白酶K　； 參考：《華中科技大學(xué)》2016年博士論文

【摘要】：第一部分血漿組織蛋白酶L、K和V含量與腹主動(dòng)脈瘤危險(xiǎn)度關(guān)系目的組織蛋白酶L (CatL)、組織蛋白酶K (CatK)以及組織蛋白酶V (CatV)作為潛在的彈性蛋白酶參與人動(dòng)脈壁重塑。本文的目的是觀測(cè)在腹主動(dòng)脈瘤(AAA)患者的血漿中這些組織蛋白酶是否發(fā)生改變。方法476名男性AAA患者作為實(shí)驗(yàn)組,200名年齡匹配的男性作為對(duì)照組。取血漿并用ELISA檢測(cè)CatL、CatK和CatV的濃度。t檢驗(yàn)、ROC曲線明確實(shí)驗(yàn)組和對(duì)照組之間是否存在差異。皮爾森相關(guān)分析檢驗(yàn)CatL與AAA疾病相關(guān)危險(xiǎn)因素之間的關(guān)系。邏輯回歸分析驗(yàn)證血清學(xué)指標(biāo)是否能作為疾病的獨(dú)立預(yù)測(cè)指標(biāo)。結(jié)果t檢驗(yàn)發(fā)現(xiàn)AAA病人血漿中CatL的含量高于對(duì)照組人群(p0.0001),而CatK和CatV含量在AAA病人中降低(P=0.052, P=0.025). ROC曲線分析再次證實(shí)了CatL的含量在AAA病人血漿中表達(dá)增高具有統(tǒng)計(jì)學(xué)意義(p0.001)。在潛在的混雜性因素中,吸煙、血管緊張素轉(zhuǎn)化酶(ACE)抑制劑、阿司匹林、氯吡格雷和他汀的使用與血漿CatL含量密切相關(guān)。皮爾森相關(guān)分析指出血漿CatL與組織蛋白酶S (CatS)(r=0.43,P0.0001)、體重指數(shù)(BMI)(r=0.07,P=0.047)以及最大動(dòng)脈直徑(r=0.29,P0.001)呈正比例增加；而與最低踩臂指數(shù)(ABI)呈負(fù)相關(guān)(r=0.22,p0.001)。用偏相關(guān)分析對(duì)上述可能的混雜因素進(jìn)行校正后,血漿CatL與CatS (r=0.43,P0.0001)、最大動(dòng)脈直徑(r=0.212,P0.001)仍具有正相關(guān),與最低ABI呈負(fù)相關(guān)(r=0.10,P=0.011)。多元邏輯回歸分析提示在對(duì)上述相同的混雜因素進(jìn)行校正前后(優(yōu)勢(shì)比(OR)分別為OR=3.04, P0.001、OR=2.42, p0.001)均提示血漿CatL為AAA的危險(xiǎn)因子。結(jié)論血漿中CatL的含量與動(dòng)脈直徑大小、最低踝臂指數(shù)(ABI)的相關(guān)性提示這種半胱氨酸蛋白酶在人外周動(dòng)脈疾病和AAA中發(fā)揮重要作用。第二部分血漿炎癥因子含量與腹主動(dòng)脈瘤危險(xiǎn)度關(guān)系目的AAA斑塊中有大量的炎癥細(xì)胞浸潤(rùn),以分泌炎性因子并促進(jìn)動(dòng)脈瘤進(jìn)展為特征。本文的目的是檢測(cè)外周血細(xì)胞因子的含量是否能夠預(yù)測(cè)AAA的危險(xiǎn)程度。方法476名男性AAA患者作為實(shí)驗(yàn)組,200名年齡匹配的男性作為對(duì)照組。取血漿并用ELISA檢測(cè)白介素6(IL-6)、白介素10(IL-10)、白介素17A (IL-17A)、Y干擾素(IFN-Y)和C反應(yīng)蛋白(CRP)的濃度。結(jié)果AAA病人血漿中IL-6、IFN-γ、IL-10和IL-17A含量較對(duì)照組低,而CRP含量高于對(duì)照組。IL-10的濃度與IFN-γ、IL-17A、IL-6呈正比,但與CRP無(wú)關(guān);此外,IL-10的濃度與收縮壓呈負(fù)相關(guān),而CRP與舒張壓、體重指數(shù)(BMI)呈正比。CRP是AAA的獨(dú)立危險(xiǎn)因子并與動(dòng)脈直徑呈正相關(guān)。IFN-γ、IL-17A和CRP與AAA橫截面積呈正相關(guān)。IL-10與AAA生長(zhǎng)速率呈正相關(guān)。AAA病人外周血CRP高于均數(shù)時(shí)動(dòng)脈瘤死亡的危險(xiǎn)性會(huì)增加。結(jié)論AAA病人中IFN-γ、IL-10、IL-17A含量減少,IFN-γ和IL-17A與AAA橫截面積呈正相關(guān),IL-10與AAA生長(zhǎng)速率、IFN-γ、IL-17A呈正相關(guān),提示Th1、Th2和Th17細(xì)胞免疫反應(yīng)參與了人AAA發(fā)病機(jī)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.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R543.16

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2 吳s，

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