过敏性紫癜急性期患儿血清IL17、MMP9的变化及意义

河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师(或指导小组)的指导下，由本人独立完成。本学位论文研究所获得的研究成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公开和使用。凡发表与学位论文主要内容相关的论文，第一署名为单位河北医科大学，试验材料、原始数据、申报的专利等知识产权均归河北医科大学所有。否则，承担相应法律责任。研究生签名：绻乔撖导师签章：场磊论二级学河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研究工作及取得的研究成果，除了文中特别加以标注和致谢等内容外，文中不包含其他人已经发表或撰写的研究成果，指导教师对此进行了审定。本论文由本人独立撰写，文责自负。研究生签名：螽葡蚴 导师签章：编罨呛捌多年弓月矽日目 录中文摘要1英文摘要4研究论文过敏性紫癜急性期患儿血清IL17、MMP9的变化及意义前言8日U舌”一“”“”“”8材料与方法9结果1 3附图，1 5附表20讨论一一一一”一一”2 1结论24参考文献26综述 IL17与血管炎性疾病关系的研究28致谢38个人简历39中文摘要过敏性紫癜急性期患儿血清IL17、MMP。9的变化及意义摘 要目的：过敏性紫癜(HenochSchonlein purpura，HSP)是儿童时期最常见的一种免疫介导的全身性血管炎性疾病，是否合并肾脏受累，直接影响到过敏性紫癜的远期预后，其发病机制目前尚不明确，因此也没有有效的防御措施防止HSP出现肾脏受累。大量的研究显示HSP及HSPN的发病机制主要为体液及细胞免疫的异常，凝血与纤溶紊乱，基因多态性改变，炎症介质的参与，同时细胞因子也发挥着重要作用。IL一17是新近发现的一种前炎性细胞因子，在多种免疫性血管炎性疾病中发挥着重要的作用，目前对于它的拮抗剂是否应用到临床来治疗自身免疫性疾病也成为研究的热点。过敏性紫癜也是一种自身免疫性血管炎，本研究进一步探讨过敏性紫癜急性期患儿血清IL17、基质金属蛋白酶9(脚9)的水平变化，同时观察两者是否具有相关性，并对过敏性紫癜患儿随访6个月，观察其肾脏是否受累，进一步了解IL17、MMP9在HSPHSPN中的发病机制，从而为如何积极治疗及采取干预措施防止HSP出现肾脏受累提供理论依据。方法：1研究对象所选病例为20123月-20127月河北省儿童医院肾脏免疫科住院的过敏性紫癜初诊患儿74例。其中男38例，女36例，年龄312岁。HSP的临床诊断依据诸福棠实用儿科学中的诊断标准；过敏性紫癜性肾炎的临床诊断依据中华医学会儿科学分会肾脏病学组制定的诊断标准，在过敏性紫癜病程中(多数在6个月内)，出现肾实质受累(血尿和或蛋白尿)，排除其他导致血尿及蛋白尿的肾脏疾病。2实验分组：(1)过敏性紫癜组：过敏性紫癜急性期患儿(符合诸福棠实用儿科学中HSP的诊断标准)：均为首次发病，1周以内未用过肾上腺皮质激素及免疫抑制剂治疗，排除既往自身免疫性疾病及过敏性疾病史；同时依据临床表现分为单纯型、关节型、腹型及混合型。 (2)非紫癜肾组和紫癜肾组：密切随访入组患儿6个月，根据是否有肾脏受累分为非紫癜肾组和紫癜肾组。(3)对照组：选择同期30例年龄、性别相匹中文摘要配的我院儿保科健康体检儿童，并排除既往自身免疫性疾病及过敏性疾病史。3检测指标及实验方法应用双抗体夹心酶联吸附试验(ELISA)检测血清IL17、MMP9的水平，操作步骤严格按试剂盒说明书进行。同时分析IL17与MMP一9是否存在相关性。所测标本均为HSP急性期患儿的血清。应用SPSS 130软件进行统计学分析，采用均数-4-标准差表示，临床资料各组间统计学方法为t检验、方差分析秩和检验，并对有关趋势变量采用线性相关分析，以P005代表有显著性差异。结果：1过敏性紫癜急性期患儿血清IL一17(8659+3550)PgmL一1明显高于健康对照组(6238+1465)PgmL1(PO01)。2过敏性紫癜急性期患儿血清MMP9(20 182士1 0587)ngmL1明显高于健康对照组【(8927士2799)ngmL1(PO05)。4过敏性紫癜急性期患儿血清各型之间MMP9水平比较显示：混合型MMP9水平比单纯型、关节型、腹型均高(氏O05)，单纯型、关节型、腹型之间MMP9水平比较均无差异。5紫癜肾组在HSP急性期血清IL1710167+3955)PgmL-1】明显高于非紫癜肾组(8138+3279)PgmL一1比较明显升高(氏O05)。6紫癜肾组在HSP急性期血清MMP一9(24963士9757)ngrnL-1Ft韭J显高于非紫癜肾组(18530-土10439)ngmL一11(9005)，即IL一17与MMP一9无相关性。结论：本研究数据显示：IL17、VlMP。9在急性期均参与HSP的发病过程，并且出现肾脏受累的患)Ltt,没有出现肾脏受累的患儿在急性期这两个值更高，说明IL17、MMP9在HSP的早期己起作用，从而提示我们要早期采取干预措施，防止HSP出现肾脏受累。不同临床类型HSP血清IL一17水平无显著性差异，说明不同临床类型的HSP并没有表现出IL17参与炎症反应的不同。我们发现过敏性紫癜组中的混合型血清MMP9水平比单纯型、关节型、腹型均高(氏O05)，单纯型、关节型、腹型MMP9中文摘要水平比较均无差异，说明混合型HSP血管损伤更严重，可能更易出现肾脏受累。同时对IL一17与MMP9的相关性分析未发现两者具有相关性(1-=01 84，P005)。关键词：过敏性紫癜；IL17；基质金属蛋白酶9(MMP一9)英文摘要The Variation and Significance of Serum Interleukin一17 andMatrixmetalloproteinase一9 of childdren in acute phase ofHenochSchonlein purpuraABSTRACTobjective：Henoch。Schonlein purpura iS the most common kind ofimmune mediated systemic vasculitis in childhood，whether to merge kidneyinvolvement，that directly affect the longterm prognosis of HenochSchonleinpurpura，its pathogenesis is still not clear,SO there is also no effective defensemeasures to prevent HSP emerging kidney involvemengtA large number ofstudies has shown that pathogenesis of HSP and HSPN is mainly for thehumoral and cellular immune abnormalities，blood coagulation andfibrinolytic disorders，change of gene polymorphism，participation ofinflammation medium，and cytokines aslo play an important roleIL一1 7 is anewly found kind of proinflammatory cytokines，plays an important role in avariety of immune vasculitis，whether its antagonist Can applly to the clinicaltreatment of autoimmune diseases has become a research hot spotAsHenochSchonlein purpura is aslo a kind of autoimmune vasculitis，this studyfurther investigate the 1evel variation of serum IL一1 7 and matrixmetalloproteinasesnine(MMP9) in childhood in acute phase ofHenochSchonlein purpura，and observe whether they have correlation，andHenochSchonlein purpura childhood are followed up for 6 months，to observewhether the kidney is affected，and then we can have a deeper understandingof the IL1 7 and MIVIP-9 in the pathogenesis of HSPHSPNProvidingtheoretical basis for how to adopt active treatment and take interventionmeasures to prevent HSP emerging kidney involvemengtMethods：1The research obj ect Senventy four cases of hospitalized children inacute phase of HenochSchonlein purpura from March 20 1 2 to July 20 1 2 inHebei Province ChildrenS Hospital in Nephroloy and Immunology departmant4英文摘要are included in this studyAmong them，3 8 are male and 3 6 are female，aged 3to 1 2 years oldThe clinical diagnosis of HSP is based on the criteria definedby theZhuFuTang practical pediatrics；The clinical diagnosis of HSPN isbased on the criteria defined by the Chinese medical association branch ofkidney disease of Pediatrics，in the course of Henoch-Schonlein purpura(mostin 6 months)，the occurrence of renal parenchyma involvement(hematuriaandor proteinuria)，and excluding other kidney disease which Can causehematuria and proteinuria2Experimental group(1)HenochSchonlein purpura group：Childhoods in acute phase ofHenochSchonlein purpura(according the diagnostic criteria of Zhu FuTang Practical Pediatrics in HSP )：adrenal corticosteroids andimmunosuppressants treatment are notused within one week，and excludeprevious autoimmune diseases or allergic disease history；based on the clinicalmanifestations，they are divided into simple type，j oints，abdominal and mixedtype(2)Non-HSPN group and HSPN group：closing followup the included groupof children 6 months，depending on whether the kidney was involved，theywere devided into non-HSPN group and HSPN group ?(3)Control group：Recruited same period of 30 healthy children who areexaminated in Our hospital of Child Health Division，ageand sexmatched，and excluded previous autoimmune disease and allergic disease history3Detection indicators and experimental methods：The serum of IL一1 7 andMMP一9 levels are detected by Enzymelinked immunosorbent assay(ELISA)，also analyze the correlation of IL一1 7 and MMP一9The detection indicators areserum specimens of children with acute HSR SPSS 1 30 software is used forstatistical analysis，the levels were expressed as mean+semThe comparisonsbetween groups used the T test，oneway ANOVA and MannWhitneyAnd thetrend variables were using linear correlation analysisA twotailed P valueof005 was considered significant difference，or considered no significantdi仟erence5英文摘要Results：1The concentration serum IL一1 7 is significantly higher in childhood inacute phase of HenochSchonlein purpura than in healthy control group(8659 4-3550 VS6238 4-1465)PgmL一1，PO01)2The concentration serum MMP-9 is significantly higher in childhoodin acute phase of HenochSchonlein purpura than in healthy control group(20182 4-10587 VS8927 4-2799)ngmLl，PO05)4The serum MMP一9 level between the various types ofHenoch-Schonlein purpura in acute phase display：Mixed type was higherthan simple、joints、abdominal妒O05)，while between simple type、j oints and abdominal the MMP一9 level shows no difference5In acute phase of liSP，the serum IL-1 7 level is significantly higher inHSPN group than nonHSPN group(10167士3955 vs 8138 4-3279)pgmL一1,P0105)6The serum MMP一9 level is significantly higher in HSPN group thannonHSPN group(24963 4-9757 VS 18530 4-10439 ngmL一1，P005)，whichexlpains that there is no correlation between IL一1