頸動脈參數(shù)和CXCL16在原發(fā)性腎病綜合征兒童中的變化及意義
發(fā)布時間：2018-07-16 11:11
【摘要】：研究背景與研究目的：原發(fā)性腎病綜合征(PNS)是小兒泌尿系統(tǒng)常見疾病之一。它的主要臨床表現(xiàn)是大量蛋白尿,低白蛋白血癥,高脂血癥以及水腫。其中大量蛋白尿、低白蛋白血癥及高脂血癥都是發(fā)生動脈粥樣硬化(AS)的危險因素。AS是成人腎病綜合征患者的常見并發(fā)癥,兒童PNS患者發(fā)生有臨床癥狀的AS者很少。因此如何早期識別AS的風險并采取積極有效的措施阻止其發(fā)展至AS是我們關(guān)注的重點,而且目前國內(nèi)外尚無研究報道。目前AS的發(fā)病機制并不十分清楚,特別是腎病綜合征并發(fā)AS的機制更需要進一步研究。AS是一種慢性炎癥性疾病,免疫反應(yīng)參與其發(fā)病機制。趨化因子是一組具有趨化功能的細胞因子,它參與炎癥及免疫應(yīng)答過程。趨化因子配體16(CXCL16)又稱作SR-PSOX,是一種CXC家族可溶性趨化因子,存在可溶性蛋白和跨膜蛋白兩種形式,它同時具有趨化、粘附、細胞表面清道夫受體的作用�？扇苄缘腃XCL16可以作為趨化因子,趨化CXCR6+細胞,包括CD4+T細胞、CD8+T細胞、NK細胞等。膜結(jié)合型CXCL16可以作為粘附分子和清道夫受體發(fā)揮作用。作為粘附分子,CXCL16能夠促進CXCR6+細胞結(jié)合并粘附到相應(yīng)的細胞或者組織；作為清道夫受體,它能夠介導磷酯酰絲氨酸和氧化低密度脂蛋白(oxLDL)的內(nèi)吞。近年來研究表明,CXCL16參與多種腎臟疾病及心血管疾病的發(fā)生發(fā)展。本研究的目的是觀察PNS患兒頸動脈結(jié)構(gòu)和功能改變以及血清CXCL16的變化,探討CXCL16與AS的相關(guān)性,為PNS患兒AS早期防治方法的研究(如CXCL16靶向治療)提供一定的理論依據(jù)。研究對象：選擇122例PNS患兒,其中疾病活動期組82例(疾病反復42例,初發(fā)40例),男66例,女16例,2-14歲；緩解期組40例,男32例,女8例,2-14歲。根據(jù)激素治療反應(yīng)及隨訪將疾病活動期組再次分為激素敏感組(60例)、激素依賴組(6例)及激素耐藥組(16例)；將40例初發(fā)PNS患兒再次分為激素敏感組(32例)、激素耐藥組(8例)。正常對照組選取同期在我院保健科門診體檢的正常健康兒童120例,男96例,女24例,2-14歲。各組之間性別、年齡、BMI相匹配,差異無統(tǒng)計學意義(P0.05)。研究方法：所有PNS患兒及正常對照組兒童均行頸動脈超聲檢查,測量頸動脈內(nèi)中膜厚度(cIMT)、舒張期內(nèi)徑(dD)及收縮期內(nèi)徑(sD)。計算頸動脈相關(guān)參數(shù)：血管壁運動度(ΔD)、僵硬度系數(shù)β(p)、頸動脈壓力應(yīng)變系數(shù)(Ep)、順應(yīng)性(AC)、平均管腔橫截面積(LCSA)、平均管壁橫截面積(WCSA)、平均橫截面擴張系數(shù)(DC)及增量彈性模量(Einc)。各組兒童分別采集清晨空腹靜脈血4m1,并于4℃離心收集血清。應(yīng)用全自動生化分析儀檢測各生化指標。血清白蛋白(ALB)采用溴甲酚綠法檢測；總膽固醇(TC)采用酶法測定；甘油三酯(TG)采用GPO-POD法測定；高密度脂蛋白(HDL)和低密度脂蛋白(LDL)采用直接法測定；載脂蛋白A (apo-A)、載脂蛋白B(apo-B)及脂蛋白a[Lp(a)]采用免疫比濁法測定；血清CXCL16和ox-LDL采用ELISA法測定。收集活動期組PNS患兒24小時尿液,準確記錄尿量,采用焦酚紅法測定24h尿蛋白定量。結(jié)果：1.各組兒童血脂水平比較PNS患兒疾病活動期組TC、TG、LDL、apo-A、 apo-B、Lp(a)、ox-LDL高于緩解期組和正常對照組(P0.01),并且緩解期組TC、TG、LDL、apo-B、 Lp (a)、 ox-LDL仍高于正常對照組(P0.05)。2.各組間頸動脈參數(shù)比較PNS患兒疾病活動期組cIMT、Ep、WCSA高于緩解期組和正常對照組(P0.05),且緩解期組cIMT、 WCSA仍高于正常對照組(P0.01)；疾病活動期組AD低于緩解期組和正常對照組(P0.01)；活動期組AC低于緩解期組(P0.05)；活動期組p高于正常對照組(P0.01)。疾病活動期PNS患兒中,激素依賴組、激素耐藥組cIMT高于激素敏感組(P0.01),而激素依賴組和激素耐藥組間cIMT無統(tǒng)計學差異(P0.05)。另外,40例初發(fā)PNS患兒cIMT高于正常對照組(P0.01)。3.各組血清CXCL16水平比較PNS患兒疾病活動期組血清CXCL16水平高于緩解期組和正常對照組(P0.01),且緩解期組血清CXCL16水平仍高于正常對照組(P0.01)。40例初發(fā)PNS患兒中,激素耐藥組血清CXCL16水平高于激素敏感組(P0.05)。4.各指標間相關(guān)性分析PNS患兒中血清CXCL16同TC、TG、LDL、apo-A、 apo-B、Lp(a)、ox-LDL、24h尿蛋白定量及cIMT正相關(guān)(P0.01)；同血清ALB負相關(guān)(P0.01)。cIMT同TC、TG、LDL、apo-A、 apo-B、 Lp(a)、 ox-LDL正相關(guān)(P0.01)；同血清ALB負相關(guān)(P0.01)。5.多元逐步回歸分析多元逐步回歸分析顯示,cIMT同TC、CXCL16、 Lp(a)獨立相關(guān)(R2=0.55,β=0.004,P0.01；β=0.007,P0.01；β=0.02,P=0.04)。結(jié)論：1.PNS患兒疾病活動期及緩解期血清TC、TG、LDL、apo-B、 Lp (a)、 ox-LDL均顯著升高,提示PNS患兒疾病活動期及緩解期脂質(zhì)代謝紊亂持續(xù)存在。2.PNS患兒頸動脈結(jié)構(gòu)和功能較正常對照兒童發(fā)生了顯著改變,提示PNS患兒發(fā)生AS的風險增加。疾病活動期患兒中,激素依賴組、激素耐藥組cIMT高于激素敏感組,提示激素依賴和激素耐藥患兒較激素敏感患兒發(fā)生AS的風險更大。40例初發(fā)PNS患兒的cIMT顯著高于正常對照組,提示在疾病初期PNS患兒已經(jīng)存在AS的風險。3.cIMT同TC,TG,LDL,apo-A, apo-B,Lp(a)及ox-LDL正相關(guān),且多元逐步回歸分析顯示,cIMT同TC及Lp(a)獨立相關(guān),提示脂質(zhì)代謝紊亂作為獨立危險因素加劇PNS患兒AS的風險。4.PNS患兒疾病活動期組及緩解期組血清CXCL16水平顯著升高,且相關(guān)性分析顯示PNS患兒血清CXCL16同TC、TG、LDL、apo-A、apo-B、Lp(a)、ox-LDL、24h尿蛋白定量正相關(guān),同血清ALB負相關(guān),提示CXCL16參與PNS的發(fā)病機制。5.40例初發(fā)PNS患兒中,激素耐藥組CXCL16水平高于激素敏感組,提示在疾病初期血清CXCL16或許可以作為預示激素治療效果的一個生物指標。6.血清CXCL16同cIMT正相關(guān),且多元逐步回歸分析發(fā)現(xiàn)CXCL16同cIMT獨立相關(guān),提示CXCL16參與PNS患兒AS的發(fā)病機制。
[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.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R726.9
本文編號：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.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R726.9
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2 李定良;巫相宏;;冠心病患者趨化因子CXCL16的水平測定及臨床意義[A];第十三次全國心血管病學術(shù)會議論文集[C];2011年
相關(guān)博士學位論文 前3條
1 徐煥賓;CXCL16在免疫性肝損傷中的作用[D];復旦大學;2005年
2 黃明方;CXCL16基因多態(tài)性與冠心病遺傳易感性的研究[D];第四軍醫(yī)大學;2010年
3 易桂文;CXCL16在動脈粥樣硬化中的作用及其機制研究[D];華中科技大學;2011年
相關(guān)碩士學位論文 前7條
1 王丹;頸動脈參數(shù)和CXCL16在原發(fā)性腎病綜合征兒童中的變化及意義[D];山東大學;2016年
2 朱艷姬;CXCL16在原發(fā)性腎病綜合征中的變化及其臨床意義[D];山東大學;2012年
3 魏武杰;外周血單個核細胞CXCL16的表達與急性冠脈綜合征關(guān)系的研究[D];南華大學;2007年
4 陳康玉;冠心病患者CXCL16水平的變化及其臨床意義[D];安徽醫(yī)科大學;2009年
5 姜正明;CXCL16趨化因子在冠心病患者血清中的變化[D];鄭州大學;2009年
6 趙靜;趨化因子CXCL16及其受體CXCR6在子宮內(nèi)膜癌組織中的表達及意義[D];青島大學;2013年
7 李定良;冠心病患者CXCL16的水平測定及臨床意義[D];廣西醫(yī)科大學;2011年
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