高血压心、肾损害的特异血清蛋白研究高密度脂蛋白胆固醇水平与脑血栓患者全因死亡相关

发布时间：2018-06-23 16:40

本文选题：蛋白质组 + 高血压　；参考：《北京协和医学院》2017年硕士论文

【摘要】：目的:高血压是心血管疾病的首要危险因素之一,长期缺乏有效控制的高血压能够引起冠心病、心衰等严重心血管事件,除心血管损害外,高血压还会造成脑、肾、眼等其它多个靶器官的损害,这些靶器官损害是高血压致残致死的主要原因。本研究旨在通过差异蛋白质组学的方法,采用串联质谱标签(Tandem Mass Tag,TMT)蛋白定量技术、联合液相色谱串联质谱(Liquid Chromatography-tandem mass spectrometry,LC-MS/MS)分析,比较正常组、单纯高血压组、高血压合并左心室肥厚组、高血压合并肾功能不全组的血清中低丰度蛋白质组,发现差异蛋白,鉴定可能有用的蛋白质,结合蛋白质的功能生物信息网络等研究成果,对所鉴定的蛋白质在高血压引起心、肾损伤发生发展中的作用进行分析研究。以期寻找高血压引起心、肾损伤发生和发展过程中出现的特异性差异蛋白,为高血压性左心室肥厚和高血压性肾功能不全的预防、治疗提供新思路。方法:分别各收集15份正常人、单纯高血压患者、高血压合并左心室肥厚患者、高血压合并肾功能不全患者的血清。首先进行蛋白质组分析,筛选出差异表达的蛋白(P0.05)。其次,用生物信息学方法对差异蛋白进行预测,运用GO和KEGG进行富集分析。最后,筛选出与高血压合并肾功能不全、高血压合并左心室肥厚相关的特异蛋白标志物和信号通路。结果:正常组为对照时,高血压合并左心室肥厚组有4个特异蛋白下调,与心肌肥厚相关的特异通路有PIBK-AKT信号通路和P53信号通路;高血压合并肾功能不全组有15个特异蛋白上调,与肾功能有关的特异通路有肾素-血管紧张素系统。高血压组为对照时,高血压合并左心室肥厚组有12个特异蛋白下调,2个特异蛋白上调,未发现与心肌肥厚相关的特异通路;高血压合并肾功能不全组有1个特异蛋白下调,8个特异蛋白上调,与肾功能有关的特异通路有Rap1信号通路。结论:我们发现了可能与高血压心、肾损伤相关的特异蛋白,以及其可能存在的特异信号通路,这些蛋白可能为高血压性左心室肥厚和高血压性肾功能不全的预防、治疗提供新思路。目的:已有研究表明高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)水平可以独立预测脑卒中的不良预后和复发,然而HDL-C水平与脑卒中亚型脑血栓的结局关系仍然不明确,本研究的目的是分析脑血栓患者HDL-C水平与全因死亡的相关性。方法:我们于2000年至2001年共纳入768例脑血栓患者并平均随访4.5年,其中男性489例(63.7%),平均年龄(61.6±9.2)岁。根据患者入院时HDL-C浓度四分位值将患者分为四组,即HDL-C浓度第1分位(HDL-C≤0.72mmol/L)组(Q1组,n=182),HDL-C 浓度第 2 分位(0.72HDL-C ≤ 0.86mmol/L)组(Q2 组,n=214),HDL-C浓度第 3 分位(0.86HDL-C≤1.00mmol/L)组(Q3 组,n=196),HDL-C 浓度第 4分位(HDL-C1.00mmol/L)组(Q4组,n=176)。收集患者入院时的基线资料及静脉血标本,检测血糖,甘油三酯,总胆固醇以及高密度脂蛋白胆固醇等值,终点事件定义为全因死亡。结果:768例脑血栓患者总全因死亡率为20.4%(157/768)。以Q1组为基准进行计算,Q2(16.8%,36/214)、Q3(18.9%,37/196)组患者全因死亡率低于 Q1 组(27.5%,50/182),差异均有统计学意义(P0.05),但是Q4组(19.3%,34/176)患者全因死亡率与Q1组(27.5%,50/182)相比无统计学意义(P0.05)。在调整了年龄,性别等影响预后因素后,Q2(HR=0.535,95%CI=0.343-0.835,P=0.006)、Q3(HR=0.409,95%CI=0.255-0.65,P0.001)、Q4(HR=0.497,95%CI=0.298-0.828,P=0.007)较Q1组均对脑血栓患者全因死亡具有保护作用。结论:高密度脂蛋白胆固醇水平与脑血栓患者全因死亡相关。
[Abstract]:Objective: hypertension is one of the most important risk factors for cardiovascular disease. Long-term lack of effective hypertension can cause serious cardiovascular events such as coronary heart disease and heart failure. In addition to cardiovascular damage, hypertension can cause damage to many other target organs such as brain, kidney and eye. These target organ damage is the main cause of death of hypertension. The purpose of this study was to compare the Tandem Mass Tag (TMT) protein quantitative technique and the combined liquid chromatography tandem mass spectrometry (Liquid Chromatography-tandem mass spectrometry, LC-MS/MS) analysis to compare the normal group, the simple hypertension group, the hypertension group, the left ventricular hypertrophy group, the hypertension and the kidney. The low abundance proteome in the functional group, found the differential protein, identified the possible useful proteins, combined with the functional biological information network of protein, and analyzed the role of the identified proteins in the development of heart and kidney injury in hypertension in order to find the heart and kidney damage. Specific differential proteins occurring during the course of birth and development provide new ideas for the prevention and treatment of hypertensive left ventricular hypertrophy and hypertensive renal insufficiency. Methods: the serum of 15 normal persons, simple hypertensive patients, hypertensive patients with left ventricular hypertrophy, high blood pressure combined with renal insufficiency were first carried out. Protein group analysis, screening the differentially expressed protein (P0.05). Secondly, using bioinformatics method to predict the difference protein, using GO and KEGG for enrichment analysis. Finally, the specific protein markers and signal pathways associated with hypertension with renal insufficiency, hypertension and left ventricular hypertrophy were screened. At the time, 4 specific proteins were downregulated in the hypertension group and the left ventricular hypertrophy group. The specific pathways associated with the hypertrophy of the myocardium were PIBK-AKT signaling pathway and P53 signaling pathway. There were 15 specific up-regulated proteins in the group of hypertensive patients with renal insufficiency, and the specific pathway related to renal function was the renin angiotensin system. High blood pressure group was higher than the control group. Blood pressure combined with left ventricular hypertrophy group had 12 specific proteins down - regulation, 2 specific proteins up - regulated, no specific pathways associated with myocardial hypertrophy, 1 specific proteins down and 8 specific proteins up regulated in the group of hypertensive patients with renal insufficiency. The specific pathway related to renal function was Rap1 signaling pathway. Conclusion: we found that it may be associated with high blood pressure. Specific proteins related to heart pressure, renal injury, and its possible specific signaling pathways that may be the prevention of hypertensive left ventricular hypertrophy and hypertensive renal insufficiency, and provide new ideas for treatment. Objective: studies have shown that high density lipoprotein cholesterol (HDL-C) levels are available. The prognosis and recurrence of cerebral apoplexy were predicted independently. However, the relationship between the HDL-C level and the outcome of cerebral thrombotic central cerebral thrombosis was still unclear. The purpose of this study was to analyze the correlation between HDL-C level and total cause of death in patients with cerebral thrombosis. Methods: We included 768 patients with cerebral thrombosis from 2000 to 2001 and were followed up for an average of 4.5 years, of which men were followed. 489 cases (63.7%), average age (61.6 + 9.2). The patients were divided into four groups according to the HDL-C concentration four at admission, that is, HDL-C concentration first (HDL-C < 0.72mmol/L) group (Q1 group, n=182), HDL-C concentration second (0.72HDL-C < < 0.86mmol/L) group (Q2 group, n=214), HDL-C concentration third sub group HDL-C concentration fourth (HDL-C1.00mmol/L) group (group Q4, n=176). Baseline data and venous blood samples were collected at admission to the patients. Blood glucose, triglycerides, total cholesterol, and high density lipoprotein cholesterol were measured. The end event was defined as all cause death. Results: Total Total cause mortality in 768 patients with cerebral thrombosis was 20.4% (157/768). Group Q1 The total cause mortality of Q2 (16.8%, 36/214), Q3 (18.9%, 37/196) group was lower than that of group Q1 (27.5%, 50/182), and the difference was statistically significant (P0.05), but there was no statistical significance between Q4 group (19.3%, 34/176) and Q1 group (27.5%, 50/182). .535,95%CI=0.343-0.835, P=0.006), Q3 (HR=0.409,95%CI=0.255-0.65, P0.001), Q4 (HR=0.497,95%CI=0.298-0.828, P=0.007) have protective effects on all cause deaths in patients with cerebral thrombosis. Conclusion: high density lipoprotein cholesterol levels are associated with all causes of death in patients with cerebral thrombosis.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3;R544.1

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