颈动脉参数和CXCL16在原发性肾病综合征儿童中的变化及意义
发布时间：2018-07-16 11:11
【摘要】：研究背景与研究目的：原发性肾病综合征(PNS)是小儿泌尿系统常见疾病之一。它的主要临床表现是大量蛋白尿,低白蛋白血症,高脂血症以及水肿。其中大量蛋白尿、低白蛋白血症及高脂血症都是发生动脉粥样硬化(AS)的危险因素。AS是成人肾病综合征患者的常见并发症,儿童PNS患者发生有临床症状的AS者很少。因此如何早期识别AS的风险并采取积极有效的措施阻止其发展至AS是我们关注的重点,而且目前国内外尚无研究报道。目前AS的发病机制并不十分清楚,特别是肾病综合征并发AS的机制更需要进一步研究。AS是一种慢性炎症性疾病,免疫反应参与其发病机制。趋化因子是一组具有趋化功能的细胞因子,它参与炎症及免疫应答过程。趋化因子配体16(CXCL16)又称作SR-PSOX,是一种CXC家族可溶性趋化因子,存在可溶性蛋白和跨膜蛋白两种形式,它同时具有趋化、粘附、细胞表面清道夫受体的作用。可溶性的CXCL16可以作为趋化因子,趋化CXCR6+细胞,包括CD4+T细胞、CD8+T细胞、NK细胞等。膜结合型CXCL16可以作为粘附分子和清道夫受体发挥作用。作为粘附分子,CXCL16能够促进CXCR6+细胞结合并粘附到相应的细胞或者组织；作为清道夫受体,它能够介导磷酯酰丝氨酸和氧化低密度脂蛋白(oxLDL)的内吞。近年来研究表明,CXCL16参与多种肾脏疾病及心血管疾病的发生发展。本研究的目的是观察PNS患儿颈动脉结构和功能改变以及血清CXCL16的变化,探讨CXCL16与AS的相关性,为PNS患儿AS早期防治方法的研究(如CXCL16靶向治疗)提供一定的理论依据。研究对象：选择122例PNS患儿,其中疾病活动期组82例(疾病反复42例,初发40例),男66例,女16例,2-14岁；缓解期组40例,男32例,女8例,2-14岁。根据激素治疗反应及随访将疾病活动期组再次分为激素敏感组(60例)、激素依赖组(6例)及激素耐药组(16例)；将40例初发PNS患儿再次分为激素敏感组(32例)、激素耐药组(8例)。正常对照组选取同期在我院保健科门诊体检的正常健康儿童120例,男96例,女24例,2-14岁。各组之间性别、年龄、BMI相匹配,差异无统计学意义(P0.05)。研究方法：所有PNS患儿及正常对照组儿童均行颈动脉超声检查,测量颈动脉内中膜厚度(cIMT)、舒张期内径(dD)及收缩期内径(sD)。计算颈动脉相关参数：血管壁运动度(ΔD)、僵硬度系数β(p)、颈动脉压力应变系数(Ep)、顺应性(AC)、平均管腔横截面积(LCSA)、平均管壁横截面积(WCSA)、平均横截面扩张系数(DC)及增量弹性模量(Einc)。各组儿童分别采集清晨空腹静脉血4m1,并于4℃离心收集血清。应用全自动生化分析仪检测各生化指标。血清白蛋白(ALB)采用溴甲酚绿法检测；总胆固醇(TC)采用酶法测定；甘油三酯(TG)采用GPO-POD法测定；高密度脂蛋白(HDL)和低密度脂蛋白(LDL)采用直接法测定；载脂蛋白A (apo-A)、载脂蛋白B(apo-B)及脂蛋白a[Lp(a)]采用免疫比浊法测定；血清CXCL16和ox-LDL采用ELISA法测定。收集活动期组PNS患儿24小时尿液,准确记录尿量,采用焦酚红法测定24h尿蛋白定量。结果：1.各组儿童血脂水平比较PNS患儿疾病活动期组TC、TG、LDL、apo-A、 apo-B、Lp(a)、ox-LDL高于缓解期组和正常对照组(P0.01),并且缓解期组TC、TG、LDL、apo-B、 Lp (a)、 ox-LDL仍高于正常对照组(P0.05)。2.各组间颈动脉参数比较PNS患儿疾病活动期组cIMT、Ep、WCSA高于缓解期组和正常对照组(P0.05),且缓解期组cIMT、 WCSA仍高于正常对照组(P0.01)；疾病活动期组AD低于缓解期组和正常对照组(P0.01)；活动期组AC低于缓解期组(P0.05)；活动期组p高于正常对照组(P0.01)。疾病活动期PNS患儿中,激素依赖组、激素耐药组cIMT高于激素敏感组(P0.01),而激素依赖组和激素耐药组间cIMT无统计学差异(P0.05)。另外,40例初发PNS患儿cIMT高于正常对照组(P0.01)。3.各组血清CXCL16水平比较PNS患儿疾病活动期组血清CXCL16水平高于缓解期组和正常对照组(P0.01),且缓解期组血清CXCL16水平仍高于正常对照组(P0.01)。40例初发PNS患儿中,激素耐药组血清CXCL16水平高于激素敏感组(P0.05)。4.各指标间相关性分析PNS患儿中血清CXCL16同TC、TG、LDL、apo-A、 apo-B、Lp(a)、ox-LDL、24h尿蛋白定量及cIMT正相关(P0.01)；同血清ALB负相关(P0.01)。cIMT同TC、TG、LDL、apo-A、 apo-B、 Lp(a)、 ox-LDL正相关(P0.01)；同血清ALB负相关(P0.01)。5.多元逐步回归分析多元逐步回归分析显示,cIMT同TC、CXCL16、 Lp(a)独立相关(R2=0.55,β=0.004,P0.01；β=0.007,P0.01；β=0.02,P=0.04)。结论：1.PNS患儿疾病活动期及缓解期血清TC、TG、LDL、apo-B、 Lp (a)、 ox-LDL均显著升高,提示PNS患儿疾病活动期及缓解期脂质代谢紊乱持续存在。2.PNS患儿颈动脉结构和功能较正常对照儿童发生了显著改变,提示PNS患儿发生AS的风险增加。疾病活动期患儿中,激素依赖组、激素耐药组cIMT高于激素敏感组,提示激素依赖和激素耐药患儿较激素敏感患儿发生AS的风险更大。40例初发PNS患儿的cIMT显著高于正常对照组,提示在疾病初期PNS患儿已经存在AS的风险。3.cIMT同TC,TG,LDL,apo-A, apo-B,Lp(a)及ox-LDL正相关,且多元逐步回归分析显示,cIMT同TC及Lp(a)独立相关,提示脂质代谢紊乱作为独立危险因素加剧PNS患儿AS的风险。4.PNS患儿疾病活动期组及缓解期组血清CXCL16水平显著升高,且相关性分析显示PNS患儿血清CXCL16同TC、TG、LDL、apo-A、apo-B、Lp(a)、ox-LDL、24h尿蛋白定量正相关,同血清ALB负相关,提示CXCL16参与PNS的发病机制。5.40例初发PNS患儿中,激素耐药组CXCL16水平高于激素敏感组,提示在疾病初期血清CXCL16或许可以作为预示激素治疗效果的一个生物指标。6.血清CXCL16同cIMT正相关,且多元逐步回归分析发现CXCL16同cIMT独立相关,提示CXCL16参与PNS患儿AS的发病机制。
[Abstract]:Primary nephrotic syndrome (PNS) is one of the common diseases of the urinary system in children. Its main clinical manifestations are massive albuminuria, hypoalbuminemia, hyperlipidemia, and edema. A large number of proteinuria, hypoalbuminemia and hyperlipidemia are the risk factors for atherosclerosis (AS),.AS is The common complications of the patients with nephrotic syndrome, there are few AS in children with PNS, so how to identify the risk of AS early and take active and effective measures to prevent it from developing to AS is the focus of our attention, and there is no research report at home and abroad. At present, the pathogenesis of AS is not very clear, especially the kidney. The mechanism of disease syndrome complicated with AS needs further study of.AS as a chronic inflammatory disease. The immune response is involved in its pathogenesis. Chemokine is a group of chemokines with chemotaxis, which is involved in the process of inflammation and immune response. Chemokine ligand 16 (CXCL16), also known as SR-PSOX, is a CXC family of soluble chemokines. There are two forms of soluble protein and transmembrane protein, which also have chemotaxis, adhesion, and cell surface scavenger receptors. Soluble CXCL16 can be used as chemokines to chemotaxis CXCR6+ cells, including CD4+T cells, CD8+T cells, NK cells and so on. Membrane binding CXCL16 can act as a adhesion molecule and the scavenger receptor. Adhesion molecules, CXCL16 can promote CXCR6+ cells to bind and adhere to the corresponding cells or tissues; as the scavenger receptor, it can mediate the endocytosis of phosphonyl serine and oxidized low density lipoprotein (oxLDL). In recent years, studies have shown that CXCL16 is involved in the development of a variety of renal diseases and cardiovascular diseases. The purpose of this study is to study the purpose of this study. The changes in the structure and function of carotid artery and the changes of serum CXCL16 were observed in children with PNS, and the correlation between CXCL16 and AS was discussed. The study provided a certain theoretical basis for the early AS prevention and control methods of PNS children (such as CXCL16 targeted therapy). 122 cases of PNS children were selected, including 82 cases of disease active phase group (42 cases of disease repeated, 40 cases first onset), and 66 males. 16 cases, 2-14 years of age, 40 cases of remission group, 32 men, 8 women, 2-14 years old. According to the hormone therapy reaction and follow-up, the disease active period group was again divided into hormone sensitive group (60 cases), hormone dependence group (6 cases) and hormone resistance group (16 cases), and 40 cases of initial PNS children were divided into hormone sensitive group (32 cases), hormone resistance group (8 cases). Normal control group. 120 normal healthy children, 96 men, 24 women, 2-14 years old, were selected in the health care department of our hospital for the same period. The sex, age and BMI were matched between each group. The difference was not statistically significant (P0.05). All the children in PNS and the normal control group were examined by carotid hyper sound, the thickness of the carotid artery was measured (cIMT), and the diastolic period was in the diastolic period. Diameter (dD) and systolic diameter (sD). Calculation of carotid artery related parameters: vascular wall motion (delta D), stiffness coefficient beta (P), carotid pressure strain coefficient (Ep), compliance (AC), mean lumen cross section area (LCSA), mean transverse section area (WCSA), average cross section dilatation coefficient (DC) and incremental elastic modulus (Einc). Children of each group were collected, respectively. 4m1 in the morning venous blood was collected and collected at 4 degrees centigrade. The biochemical indexes were detected by automatic biochemical analyzer. Serum albumin (ALB) was detected by bromo methyl phenol green method; total cholesterol (TC) was determined by enzyme method; triglyceride (TG) was determined by GPO-POD; high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by direct method. It was determined that apolipoprotein A (apo-A), apolipoprotein B (apo-B) and lipoprotein a[Lp (a)] were determined by immunoturbidimetry; serum CXCL16 and ox-LDL were determined by ELISA method. The urine volume was recorded for 24 hours in children with PNS in active phase group, the urine volume was recorded accurately, and the quantity of 24h urine was measured by focal phenol red method. Results: the blood lipid levels in 1. groups were compared with those of children with PNS. TC, TG, LDL, apo-A, apo-B, Lp (a), ox-LDL higher than the remission group and the normal control group (P0.01), and the remission group was higher than the normal control group, which was still higher than the normal control group. Phase group cIMT, WCSA still higher than normal control group (P0.01), AD in disease active stage was lower than that of remission group and normal control group (P0.01), AC in active phase group was lower than that of remission group (P0.05), P in active phase group was higher than that of normal control group (P0.01). Hormone dependence group, hormone resistance group cIMT was higher than hormone sensitive group (P0.01), and irritable period in the disease active period PNS children. There was no statistical difference between the cIMT group and the hormone resistant group (P0.05). In addition, the serum CXCL16 level of 40 children with primary PNS was higher than that of the normal control group (P0.01).3.. The serum CXCL16 level of the disease active stage group was higher than that of the remission group and the normal control group (P0.01), and the serum CXCL16 level in the remission group was still higher than that of the normal control group. Group (P0.01).40 patients with primary PNS, the level of serum CXCL16 in the hormone resistant group is higher than that of the hormone sensitive group (P0.05).4.. Ox-LDL positive correlation (P0.01), ALB negative correlation with serum (P0.01).5. multivariate stepwise regression analysis, multivariate stepwise regression analysis showed that cIMT was independent of TC, CXCL16, Lp (a). It was suggested that the carotid artery structure and function of children with.2.PNS in the disease active period and remission period of the PNS children had a significant change in the carotid structure and function in children with the normal control, suggesting that the risk of AS in the children with PNS was increased. The hormone dependence group and the hormone tolerance group cIMT were higher than the hormone sensitive group, suggesting hormone dependence in the children with disease activity. The risk of AS in children with hormone resistance was greater than that in children with hormone sensitivity, and the cIMT of children with primary PNS was significantly higher than that of the normal control group. It was suggested that the risk of AS in children with PNS at the early stage of the disease was.3.cIMT with TC, TG, LDL, apo-A, apo-B, and positive correlation. As an independent risk factor, the risk of AS in children with PNS increased the level of serum CXCL16 in children with.4.PNS, and the correlation analysis showed that serum CXCL16 in children with PNS was associated with TC, TG, LDL, apo-A, apo-B, Lp. In the pathogenesis of NS, the level of CXCL16 in the primary PNS children is higher than that of the hormone sensitive group. The level of CXCL16 in the hormone resistant group is higher than that in the hormone sensitive group. It is suggested that the serum CXCL16 may be a biological indicator of the effect of hormone therapy at the early stage of the disease. The serum CXCL16 is positively related to cIMT, and the multivariate stepwise regression analysis shows that CXCL16 is independent of cIMT, suggesting CXCL16 participation P. The pathogenesis of AS in children with NS.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R726.9
本文编号：2126202
[Abstract]:Primary nephrotic syndrome (PNS) is one of the common diseases of the urinary system in children. Its main clinical manifestations are massive albuminuria, hypoalbuminemia, hyperlipidemia, and edema. A large number of proteinuria, hypoalbuminemia and hyperlipidemia are the risk factors for atherosclerosis (AS),.AS is The common complications of the patients with nephrotic syndrome, there are few AS in children with PNS, so how to identify the risk of AS early and take active and effective measures to prevent it from developing to AS is the focus of our attention, and there is no research report at home and abroad. At present, the pathogenesis of AS is not very clear, especially the kidney. The mechanism of disease syndrome complicated with AS needs further study of.AS as a chronic inflammatory disease. The immune response is involved in its pathogenesis. Chemokine is a group of chemokines with chemotaxis, which is involved in the process of inflammation and immune response. Chemokine ligand 16 (CXCL16), also known as SR-PSOX, is a CXC family of soluble chemokines. There are two forms of soluble protein and transmembrane protein, which also have chemotaxis, adhesion, and cell surface scavenger receptors. Soluble CXCL16 can be used as chemokines to chemotaxis CXCR6+ cells, including CD4+T cells, CD8+T cells, NK cells and so on. Membrane binding CXCL16 can act as a adhesion molecule and the scavenger receptor. Adhesion molecules, CXCL16 can promote CXCR6+ cells to bind and adhere to the corresponding cells or tissues; as the scavenger receptor, it can mediate the endocytosis of phosphonyl serine and oxidized low density lipoprotein (oxLDL). In recent years, studies have shown that CXCL16 is involved in the development of a variety of renal diseases and cardiovascular diseases. The purpose of this study is to study the purpose of this study. The changes in the structure and function of carotid artery and the changes of serum CXCL16 were observed in children with PNS, and the correlation between CXCL16 and AS was discussed. The study provided a certain theoretical basis for the early AS prevention and control methods of PNS children (such as CXCL16 targeted therapy). 122 cases of PNS children were selected, including 82 cases of disease active phase group (42 cases of disease repeated, 40 cases first onset), and 66 males. 16 cases, 2-14 years of age, 40 cases of remission group, 32 men, 8 women, 2-14 years old. According to the hormone therapy reaction and follow-up, the disease active period group was again divided into hormone sensitive group (60 cases), hormone dependence group (6 cases) and hormone resistance group (16 cases), and 40 cases of initial PNS children were divided into hormone sensitive group (32 cases), hormone resistance group (8 cases). Normal control group. 120 normal healthy children, 96 men, 24 women, 2-14 years old, were selected in the health care department of our hospital for the same period. The sex, age and BMI were matched between each group. The difference was not statistically significant (P0.05). All the children in PNS and the normal control group were examined by carotid hyper sound, the thickness of the carotid artery was measured (cIMT), and the diastolic period was in the diastolic period. Diameter (dD) and systolic diameter (sD). Calculation of carotid artery related parameters: vascular wall motion (delta D), stiffness coefficient beta (P), carotid pressure strain coefficient (Ep), compliance (AC), mean lumen cross section area (LCSA), mean transverse section area (WCSA), average cross section dilatation coefficient (DC) and incremental elastic modulus (Einc). Children of each group were collected, respectively. 4m1 in the morning venous blood was collected and collected at 4 degrees centigrade. The biochemical indexes were detected by automatic biochemical analyzer. Serum albumin (ALB) was detected by bromo methyl phenol green method; total cholesterol (TC) was determined by enzyme method; triglyceride (TG) was determined by GPO-POD; high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by direct method. It was determined that apolipoprotein A (apo-A), apolipoprotein B (apo-B) and lipoprotein a[Lp (a)] were determined by immunoturbidimetry; serum CXCL16 and ox-LDL were determined by ELISA method. The urine volume was recorded for 24 hours in children with PNS in active phase group, the urine volume was recorded accurately, and the quantity of 24h urine was measured by focal phenol red method. Results: the blood lipid levels in 1. groups were compared with those of children with PNS. TC, TG, LDL, apo-A, apo-B, Lp (a), ox-LDL higher than the remission group and the normal control group (P0.01), and the remission group was higher than the normal control group, which was still higher than the normal control group. Phase group cIMT, WCSA still higher than normal control group (P0.01), AD in disease active stage was lower than that of remission group and normal control group (P0.01), AC in active phase group was lower than that of remission group (P0.05), P in active phase group was higher than that of normal control group (P0.01). Hormone dependence group, hormone resistance group cIMT was higher than hormone sensitive group (P0.01), and irritable period in the disease active period PNS children. There was no statistical difference between the cIMT group and the hormone resistant group (P0.05). In addition, the serum CXCL16 level of 40 children with primary PNS was higher than that of the normal control group (P0.01).3.. The serum CXCL16 level of the disease active stage group was higher than that of the remission group and the normal control group (P0.01), and the serum CXCL16 level in the remission group was still higher than that of the normal control group. Group (P0.01).40 patients with primary PNS, the level of serum CXCL16 in the hormone resistant group is higher than that of the hormone sensitive group (P0.05).4.. Ox-LDL positive correlation (P0.01), ALB negative correlation with serum (P0.01).5. multivariate stepwise regression analysis, multivariate stepwise regression analysis showed that cIMT was independent of TC, CXCL16, Lp (a). It was suggested that the carotid artery structure and function of children with.2.PNS in the disease active period and remission period of the PNS children had a significant change in the carotid structure and function in children with the normal control, suggesting that the risk of AS in the children with PNS was increased. The hormone dependence group and the hormone tolerance group cIMT were higher than the hormone sensitive group, suggesting hormone dependence in the children with disease activity. The risk of AS in children with hormone resistance was greater than that in children with hormone sensitivity, and the cIMT of children with primary PNS was significantly higher than that of the normal control group. It was suggested that the risk of AS in children with PNS at the early stage of the disease was.3.cIMT with TC, TG, LDL, apo-A, apo-B, and positive correlation. As an independent risk factor, the risk of AS in children with PNS increased the level of serum CXCL16 in children with.4.PNS, and the correlation analysis showed that serum CXCL16 in children with PNS was associated with TC, TG, LDL, apo-A, apo-B, Lp. In the pathogenesis of NS, the level of CXCL16 in the primary PNS children is higher than that of the hormone sensitive group. The level of CXCL16 in the hormone resistant group is higher than that in the hormone sensitive group. It is suggested that the serum CXCL16 may be a biological indicator of the effect of hormone therapy at the early stage of the disease. The serum CXCL16 is positively related to cIMT, and the multivariate stepwise regression analysis shows that CXCL16 is independent of cIMT, suggesting CXCL16 participation P. The pathogenesis of AS in children with NS.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R726.9
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2 朱艳姬;CXCL16在原发性肾病综合征中的变化及其临床意义[D];山东大学;2012年
3 魏武杰;外周血单个核细胞CXCL16的表达与急性冠脉综合征关系的研究[D];南华大学;2007年
4 陈康玉;冠心病患者CXCL16水平的变化及其临床意义[D];安徽医科大学;2009年
5 姜正明;CXCL16趋化因子在冠心病患者血清中的变化[D];郑州大学;2009年
6 赵静;趋化因子CXCL16及其受体CXCR6在子宫内膜癌组织中的表达及意义[D];青岛大学;2013年
7 李定良;冠心病患者CXCL16的水平测定及临床意义[D];广西医科大学;2011年
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