血清SIRT3、Endocan与原发性高血压及靶器官损害的相关性研究
发布时间：2018-10-23 06:58
【摘要】：背景:高血压病是一种由多种基因突变和环境因素互相作用为结果,以动脉血压持续增高为特点的慢性心血管疾病。高血压病的持续进展加速靶器官损害,从而导致心脑肾器官的衰竭。根据2010年中国高血压防治指南,高血压引起的无症状靶器官损害定义为:左心室肥厚,超声心动图左室质量指数(LVMI):男≥125g/m2,女≥120g/m2;颈动脉内膜中层厚度(IMT)≥0.09mm或动脉粥样斑块;颈-股动脉脉搏波速度≥12m/s或肱踝脉搏波传导速度(BaPWV)≥14m/s;踝/臂血压指数0.9等。近年来高血压合并靶器官损害的发生率日趋增高,左心室肥厚的高血压患者易发生心脏缺血,心律失常或猝死。有研究表明,劲动脉内膜中层厚度增厚和斑块形成与高血压等危险因素密切相关。高血压合并靶器官损害显著增加患者的死亡风险和经济负担,降低患者的生活质量。颈动脉超声可作为"窥视"全身动脉粥样硬化进展的一个窗口。经胸超声心动图、颈动脉超声及脉搏波速度是目前筛查高血压合并靶器官损害较常用的方法。SIRT3(Sirtuins3),一类依赖NAD+辅酶的去乙酰化酶家族成员之一,近年来备受关注。研究发现SIRT3参与了多种细胞进程,包括细胞增殖、细胞自噬、细胞代谢、寿命基因的调控以及抑制肿瘤。最新发现小鼠SIRT3通过改善脂质代谢紊乱从而抑制心肌肥厚。然而,高血压合并靶器官损害患者中SIRT3的表达情况是否异常未有报道。Endocan(ESM-1),由血管内皮细胞分泌的特异性糖蛋白,是参与维持内皮功能稳态的重要因子之一。近年研究发现endocan与炎症、血管重构、凝血机制、肿瘤侵入有关。也有学者报道其与心血管疾病的关系,升高的血清endocan水平可能是动脉硬化发展的迹象之一。目前SIRT3与endocan在原发性高血压疾病中的研究极少,而高血压合并$靶器官损害患者中SIRT3与endocan的表达水平未曾有报道。本研究通过ELISA技术检测高血压患者血清中SIRT3和endocan水平,结合经胸超声心动图、颈动脉超声和PWV检查,综合评估血清SIRT3与endocan在原发性高血压患者的变化,并探讨其与高血压合并靶器官损害的相关性。研究目的:1.研究血清SIRT3、endocan与原发性高血压病的相关性。2.探讨血清SIRT3、endocan与高血压合并靶器官损害的相关性。3.评估血清SIRT3、endocan在原发性高血压的发生和进展中是否具有预测作用。研究方法:连续收集2015年10月至2016年11月就诊于我院心内科门诊的高血压患者85例作为病例组。经胸超声心动图和颈动脉彩超将病例组分为高血压合并靶器官损害组(target-organ damage,TOD)和高血压无靶器官损害组(non-target-organ damage,NTOD)。收集同期门诊健康者47例作为正常对照组(control)。本研究已通过医院伦理委员会,病例组及对照组均签署知情同意书。完成病史采集及一般情况测量,包括血压、身高、体重。并抽取空腹静脉血4ml(EDTA抗凝),应用ELISA方法测定血清SIRT3和endocan水平。三组进行彩超及PWV检查,测量颈总动脉收缩期内径及舒张期内径,颈动脉内膜中层厚度,评估斑块及斑块积分,测量各个心腔结构的大小,着重记录左室内径,左室后壁厚度,舒张末期室间隔厚度等;使用VP1000测量脉搏波传导速度及踝臂指数等。应用SPSS20软件包进行统计学处理,正态分布计量资料皆以均数±标准误(mean±SEM)表示,多组间比较采用单因素方差分析,有差异之后的两两比较采用最小显著性差异法(LSD),排除影响因素比较使用协方差分析,主效应对比采用最小显著性差异法。相关性分析采用偏相关分析,回归分析采用多元线性回归分析。指标均以P0.05为具有统计学差异。研究结果:1.一般资料显示,TOD组、NTOD组与control组在年龄(Age)、性别(Sex)、体重指数(BMI)、血糖、肌酐、尿素氮(BUN)、甘油三酯(TG)等危险因素无显著性差异(P0.05)。而在收缩压(SBP)、舒张压(DBP)、高密度脂蛋白(HDLC)、低密度脂蛋白(LDLC)、尿酸(UA)等均有明显差异(P0.05)。2.颈动脉超声和BaPWV结果显示:TOD组的颈动脉内膜中层厚度(IMT)、颈动脉舒张期内径(Dd)、颈动脉收缩期内径(Ds)、颈动脉僵硬度(SC)、肱踝脉搏波速度(BaPWV)明显高于NTOD组与control组,而颈动脉紧张度(Strain)和颈动脉扩张性系数(DC)明显低于后两组(P0.05)。3.超声心动图结果显示:TOD组的室间舒张末期室间隔厚(IVSTd)、舒张末期左室内径(LVIDd)、左室后壁舒张期厚度(LVPWTd)和左室质量指数(LVMI)均大于 NTOD 和 control 组(P0.05)。4.TOD组血清SIRT3水平远低于NTOD组和control组(P0.05)。TOD组血清endocan水平远高于NTOD组和control组(P0.05)。5.所有患者中,血清SIRT3水平与左室质量指数、颈动脉内膜中层厚度、肱踝脉搏波速度显著负相关(r=-0.331,P0.001;r=-0.314,P0.001;r=-0.473,P0.001)。血清endocan水平与左室质量指数、颈动脉内膜中层厚度、肱踝脉搏波速度显著正相关(r=0.233,P0.01;r=0.219,P0.05;r=0.188,P0.05)。结论:1.高血压合并靶器官损害组血清SIRT3水平低于高血压无靶器官损害组及对照组,提示SIRT3可能在高血压及靶器官损害的发生发展中起保护作用。2.高血压合并靶器官损害组血清endocan水平高于高血压无靶器官损害组及对照组,提示endocan促进高血压及靶器官损害的发展,可以为临床治疗提供新的治疗靶点。3.血清SIRT3、endocan水平在高血压及靶器官损害的发展中呈负相关,其因果关系有待进一步研究。
[Abstract]:Background: Hypertension is a chronic cardiovascular disease characterized by a variety of genetic mutations and environmental factors interacting with each other as a result. The sustained progression of hypertension accelerates the target organ damage, leading to failure of the renal organ of the liver. According to the guidelines for prevention and cure of hypertension in China in 2010, asymptomatic target organ damage caused by hypertension was defined as left ventricular hypertrophy, echocardiographic left ventricular mass index (LVMI): male tongue 125g/ m2, female gametocyte 120g/ m2, intima-media thickness (IMT) of carotid artery 0.09mm or atherosclerosis plaque; The pulse wave velocity of the neck-femoral artery was 12m/ s or the brachial ankle pulse wave conduction velocity (BaPWV) was 14m/ s; the ankle/ arm blood pressure index was 0. 9 and so on. In recent years, the incidence of hypertension combined with target organ damage is increasing, and hypertension patients with left ventricular hypertrophy are prone to cardiac ischemia, arrhythmia or sudden death. It has been shown that the thickening of middle layer thickness and plaque formation are closely related to the risk factors such as hypertension. High blood pressure combined with target organ damage significantly increases the risk of death and economic burden of patients, and decreases the quality of life of patients. Carotid ultrasound can be used as peephole A window of progression of systemic atherosclerosis. Transthoracic echocardiography, carotid ultrasound and pulse wave velocity are commonly used methods for screening high blood pressure combined target organ damage. SIRT3 (Sirtuins3), one of the members dependent on NAD + coenzyme, has attracted much attention in recent years. The study found that SIRT3 was involved in various cell processes, including cell proliferation, cell autophagy, cell metabolism, longevity gene regulation and tumor suppression. Recently, SIRT3 has been found to inhibit myocardial hypertrophy by improving lipid metabolism disorder. However, the abnormal expression of SIRT3 in patients with hypertension and target organ damage was not reported. Endoderm (OPG-1), a specific glycoprotein secreted by vascular endothelial cells, is one of the important factors involved in maintaining the homeostasis of endothelial function. Recent studies have found endocan associated with inflammation, vascular remodeling, coagulation mechanisms, and tumor invasion. Some scholars also reported that their relationship with cardiovascular disease, elevated serum endosan levels, could be one of the signs of atherosclerosis. At present, the study of SIRT3 and endocan in essential hypertension is very rare, while the expression level of SIRT3 and endocan in patients with hypertension complicated with $target organ damage has not been reported. In this study, the levels of SIRT3 and endosan in serum of patients with hypertension were detected by ELISA. Combined with transthoracic echocardiography, carotid ultrasound and PWV, the changes of serum SIRT3 and endocan in patients with essential hypertension were assessed. Purpose of Study: 1. To study the correlation of serum SIRT3, endocan and essential hypertension. To explore the correlation of serum SIRT3, endocan and hypertension combined with target organ damage. To assess whether serum SIRT3, endocan has a predictive role in the occurrence and progression of essential hypertension. Methods: 85 patients with hypertension from October 2015 to November 2016 were collected as case group. The cases of hypertension were combined with target organ damage group (TOD) and non-target organ damage group (NTOD) by transthoracic echocardiography and carotid ultrasound. Forty-seven out-of-patient health patients were collected as control. Informed consent was signed by the hospital ethics committee, case group and control group. Complete medical history collection and general measurement, including blood pressure, height, body weight. The serum SIRT3 and endosan levels were determined by ELISA. Three groups of color Doppler and PWV examination were performed to measure the systolic and diastolic diameter, carotid intima-media thickness of carotid artery, evaluate plaque and plaque scores, measure the size of each cardiac cavity structure, and focus on recording the left ventricular diameter, the posterior wall thickness of the left chamber, the end diastolic ventricular septal thickness, and so on. Pulse wave conduction velocity and ankle brachial index were measured using VP1000. The SPSS20 software package was used for statistical processing, and the normal distribution measurement data were expressed by means of single-factor analysis of variance (MEAN _ SEM). A single factor analysis of variance was used to compare the differences between the two groups, and the difference was used to compare the two groups with the least significant difference method (LSD). Covariance analysis was used to exclude the influence factors, and the least significant difference method was used for the main effect comparison. Multivariate linear regression analysis was used to analyze the correlation between correlation analysis and regression analysis. All the indexes were statistically different with P0.05. Results of the study: 1. In general, there was no significant difference in the risk factors such as age (Age), sex (Sex), body mass index (BMI), blood glucose (BMI), glucose (BMI), triglyceride (TG), etc. (P0.05). The systolic blood pressure (SBP), diastolic blood pressure (DBP), high density lipoprotein (HDLC), low density lipoprotein (LDLC) and uric acid (UA) were significantly different (P0.05). Carotid ultrasound and BaPWV showed that carotid intima-media thickness (IMT), carotid artery diastolic diameter (Dd), carotid systolic internal diameter (Ds), carotid stiffness (SC), brachial ankle pulse wave velocity (BPWV) were significantly higher than those in control group. Carotid artery tension and carotid expansion coefficient (DC) were significantly lower than that in the latter two groups (P0.05). The results of echocardiography showed that the interventricular septum thickness (IVSTd) and the end-diastolic left ventricular diameter (LVIDD) in the TOD group. The left ventricular diastolic thickness (LVPWTd) and the left ventricular mass index (LVMI) were all greater than those of NTOD and control group (P0.05). In all patients, the serum SIRT3 level was negatively correlated with the left ventricular mass index, carotid intima-media thickness and brachial ankle pulse wave velocity (r =-0.331, P0.001; r =-0.314, P0.001; r =-0.473, P0.001). The level of serum endocan was positively correlated with left ventricular mass index, carotid intima-media thickness and brachial ankle pulse wave velocity (r = 0.233, P0.01; r = 0.0219, P0.05; r = 0.188, P0.05). Conclusion: 1. The serum SIRT3 level of patients with hypertension complicated with target organ damage was lower than that of non-target organ damage group and control group of hypertension, suggesting that SIRT3 could play a protective role in the development of hypertension and target organ damage. The level of serum endocan in hypertensive patients with target organ damage group is higher than that of non-target organ damage group and control group of hypertension. It is suggested that endocan can promote the development of hypertension and target organ damage, and can provide new therapeutic target for clinical treatment. There was a negative correlation between the serum SIRT3 and endocan levels in the development of hypertension and target organ damage.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.11
本文编号：2288401
[Abstract]:Background: Hypertension is a chronic cardiovascular disease characterized by a variety of genetic mutations and environmental factors interacting with each other as a result. The sustained progression of hypertension accelerates the target organ damage, leading to failure of the renal organ of the liver. According to the guidelines for prevention and cure of hypertension in China in 2010, asymptomatic target organ damage caused by hypertension was defined as left ventricular hypertrophy, echocardiographic left ventricular mass index (LVMI): male tongue 125g/ m2, female gametocyte 120g/ m2, intima-media thickness (IMT) of carotid artery 0.09mm or atherosclerosis plaque; The pulse wave velocity of the neck-femoral artery was 12m/ s or the brachial ankle pulse wave conduction velocity (BaPWV) was 14m/ s; the ankle/ arm blood pressure index was 0. 9 and so on. In recent years, the incidence of hypertension combined with target organ damage is increasing, and hypertension patients with left ventricular hypertrophy are prone to cardiac ischemia, arrhythmia or sudden death. It has been shown that the thickening of middle layer thickness and plaque formation are closely related to the risk factors such as hypertension. High blood pressure combined with target organ damage significantly increases the risk of death and economic burden of patients, and decreases the quality of life of patients. Carotid ultrasound can be used as peephole A window of progression of systemic atherosclerosis. Transthoracic echocardiography, carotid ultrasound and pulse wave velocity are commonly used methods for screening high blood pressure combined target organ damage. SIRT3 (Sirtuins3), one of the members dependent on NAD + coenzyme, has attracted much attention in recent years. The study found that SIRT3 was involved in various cell processes, including cell proliferation, cell autophagy, cell metabolism, longevity gene regulation and tumor suppression. Recently, SIRT3 has been found to inhibit myocardial hypertrophy by improving lipid metabolism disorder. However, the abnormal expression of SIRT3 in patients with hypertension and target organ damage was not reported. Endoderm (OPG-1), a specific glycoprotein secreted by vascular endothelial cells, is one of the important factors involved in maintaining the homeostasis of endothelial function. Recent studies have found endocan associated with inflammation, vascular remodeling, coagulation mechanisms, and tumor invasion. Some scholars also reported that their relationship with cardiovascular disease, elevated serum endosan levels, could be one of the signs of atherosclerosis. At present, the study of SIRT3 and endocan in essential hypertension is very rare, while the expression level of SIRT3 and endocan in patients with hypertension complicated with $target organ damage has not been reported. In this study, the levels of SIRT3 and endosan in serum of patients with hypertension were detected by ELISA. Combined with transthoracic echocardiography, carotid ultrasound and PWV, the changes of serum SIRT3 and endocan in patients with essential hypertension were assessed. Purpose of Study: 1. To study the correlation of serum SIRT3, endocan and essential hypertension. To explore the correlation of serum SIRT3, endocan and hypertension combined with target organ damage. To assess whether serum SIRT3, endocan has a predictive role in the occurrence and progression of essential hypertension. Methods: 85 patients with hypertension from October 2015 to November 2016 were collected as case group. The cases of hypertension were combined with target organ damage group (TOD) and non-target organ damage group (NTOD) by transthoracic echocardiography and carotid ultrasound. Forty-seven out-of-patient health patients were collected as control. Informed consent was signed by the hospital ethics committee, case group and control group. Complete medical history collection and general measurement, including blood pressure, height, body weight. The serum SIRT3 and endosan levels were determined by ELISA. Three groups of color Doppler and PWV examination were performed to measure the systolic and diastolic diameter, carotid intima-media thickness of carotid artery, evaluate plaque and plaque scores, measure the size of each cardiac cavity structure, and focus on recording the left ventricular diameter, the posterior wall thickness of the left chamber, the end diastolic ventricular septal thickness, and so on. Pulse wave conduction velocity and ankle brachial index were measured using VP1000. The SPSS20 software package was used for statistical processing, and the normal distribution measurement data were expressed by means of single-factor analysis of variance (MEAN _ SEM). A single factor analysis of variance was used to compare the differences between the two groups, and the difference was used to compare the two groups with the least significant difference method (LSD). Covariance analysis was used to exclude the influence factors, and the least significant difference method was used for the main effect comparison. Multivariate linear regression analysis was used to analyze the correlation between correlation analysis and regression analysis. All the indexes were statistically different with P0.05. Results of the study: 1. In general, there was no significant difference in the risk factors such as age (Age), sex (Sex), body mass index (BMI), blood glucose (BMI), glucose (BMI), triglyceride (TG), etc. (P0.05). The systolic blood pressure (SBP), diastolic blood pressure (DBP), high density lipoprotein (HDLC), low density lipoprotein (LDLC) and uric acid (UA) were significantly different (P0.05). Carotid ultrasound and BaPWV showed that carotid intima-media thickness (IMT), carotid artery diastolic diameter (Dd), carotid systolic internal diameter (Ds), carotid stiffness (SC), brachial ankle pulse wave velocity (BPWV) were significantly higher than those in control group. Carotid artery tension and carotid expansion coefficient (DC) were significantly lower than that in the latter two groups (P0.05). The results of echocardiography showed that the interventricular septum thickness (IVSTd) and the end-diastolic left ventricular diameter (LVIDD) in the TOD group. The left ventricular diastolic thickness (LVPWTd) and the left ventricular mass index (LVMI) were all greater than those of NTOD and control group (P0.05). In all patients, the serum SIRT3 level was negatively correlated with the left ventricular mass index, carotid intima-media thickness and brachial ankle pulse wave velocity (r =-0.331, P0.001; r =-0.314, P0.001; r =-0.473, P0.001). The level of serum endocan was positively correlated with left ventricular mass index, carotid intima-media thickness and brachial ankle pulse wave velocity (r = 0.233, P0.01; r = 0.0219, P0.05; r = 0.188, P0.05). Conclusion: 1. The serum SIRT3 level of patients with hypertension complicated with target organ damage was lower than that of non-target organ damage group and control group of hypertension, suggesting that SIRT3 could play a protective role in the development of hypertension and target organ damage. The level of serum endocan in hypertensive patients with target organ damage group is higher than that of non-target organ damage group and control group of hypertension. It is suggested that endocan can promote the development of hypertension and target organ damage, and can provide new therapeutic target for clinical treatment. There was a negative correlation between the serum SIRT3 and endocan levels in the development of hypertension and target organ damage.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.11
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