过敏性紫癜患儿血清中IL-33及可溶性受体的表达研究
本文选题:过敏性紫癜 + 白介素33 ; 参考:《山东大学》2017年硕士论文
【摘要】:目的:检测白介素33(interleukin-33,IL-33)、IL-33可溶性ST2受体(soluble ST2,sST2)、IL-4、IL-5及IL-6在过敏性紫癜(Henoch-Schonlein purpura,HSP)患儿外周血中的表达水平,探讨其与HSP发生发展的内在联系,为疾病的靶向治疗提供理论依据。方法:选取2015年8月至2015年12月期间在山东大学附属省立医院就诊的27例HSP患儿作为实验组,22例本院同期健康体检儿童作为对照组,其中,实验组又分为初诊时的急性期组和治疗后的恢复期组。所有患儿均符合2006年欧洲抗风湿病联盟和欧洲儿科风湿病学会(EULAR/PReS)过敏性紫瘢的诊断标准,健康对照组均无近期感染史及血液系统和其他系统相关疾病史。抽取全部患者急性期、恢复期及健康对照组儿儿童外周血,采用酶联免疫吸附法(ELISA)和实时荧光定量PCR(Quantitative Real-time PCR)法检测其IL-33及sST2血清表达水平及mRNA表达量,并同时检测相关因子IL-4、IL-5及IL-6的血清水平,探讨上述因子的变化与HSP发生、发展的关系及其临床意义。结果:1.HSP患儿急性期血清IL-33水平(365.5土160.6pg/ml)明显高于恢复期IL-33(186.7± 101.5pg/ml)及正常对照组IL-33(175.9±92.8pg/ml)(P0.05),HSP患儿恢复期与正常对照组相比,IL-33水平差异无统计学意义(P0.05)。HSP患儿急性期血清35T2(1788.6±523.8pg/ml),较恢复期35T2(1182.5±455.7pg/ml)及健康对照组血清sST2(1083.6±489.6pg/m])亦有升高,但差异均无统计学意义(P0.05)。(见表2)2.HSP患儿急性期血清IL-4(20.1±14.7pg/ml)较恢复期(16.3±12.1pg/ml)及健康对照组血清IL-4(16.9±13.0pg/ml)均升高,差异有统计学意义(尸0.05),HSP恢复期与健康对照组IL-4水平无显著差异(P0.05)。HSP患儿急性期血清IL-5水平为(18.7±3.9pg/ml),较恢复期(9.7±2.9pg/ml)及健康对照组(9.1±3.2pg/ml)升高,差异有统计学意义(P0.05)。HSP患儿急性期血清IL-6水平(208.7±31.3pg/ml)明显高于恢复期(40.1 ±6.2pg/ml)及正常对照组(32.4±4.7pg/ml)(P0.05),HSP患儿恢复期与正常对照组相比,IL-6水平差异无统计学意义(P0.05)。(见表2)3.HSP患儿急性期血清sST2/IL-33比值(4.84±3.21)明显低于恢复期(6.81±3.57)及健康对照组(6.77士3.84)(P0.05),恢复期与健康对照组sST2/IL-33差异无统计学意义(P0.05)。(见图1)4.实时荧光定量PCR结果证实,HSP患儿急性期IL-33 mRNA水平较恢复期升高(5.39±2.08)倍,较正常对照组升高(5.47± 1.97)倍,差异均有统计学意义(P0.05),HSP患儿恢复期与健康对照组IL-33 mRNA水平差异无统计学意义(P0.05)。HSP患儿急性期sST2mRNA水平较恢复期升高(2.97±1.91)倍,较正常对照组升高(3.13±2.01)倍,差异均有统计学意义(P0.05)。HSP患儿恢复期与健康对照组sST2 mRNA水平差异无统计学意义(P0.05)。(见图2)5.HSP患儿急性期sST2/IL-33 mRNA比值较恢复期及健康对照组明显降低(P0.05),恢复期与健康对照组无明显差异(P0.05)。(见图3)结论:1.急性期HSP患者血清IL-33、IL-4、IL-5及IL-6水平明显高于HSP患者恢复期及正常对照组,提示这四种因子与HSP的发生发展可能存在密切关系。2.HSP患儿急性期血清sST2水平较恢复期及正常对照组轻度升高,但无统计学意义,而研究表明sST2作为诱骗受体与IL-33结合不能引起信号传导,而是阻碍IL-33/ST2信号传导,提示sST2可能作为一种保护性因素参与HSP。3.HSP患儿急性期sST2/IL-33比值较恢复期及正常对照组明显降低,说明HSP患者体内sST2/IL-33水平失衡,可能是导致HSP发生的重要原因,重塑sST2/IL-33平衡可能是治疗HSP的一个新的方向和策略。
[Abstract]:Objective: to detect the expression level of interleukin-33 (interleukin-33, IL-33), IL-33 soluble ST2 receptor (soluble ST2, sST2), IL-4, IL-5 and IL-6 in the peripheral blood of children with Henoch Schonlein purpura (Henoch-Schonlein purpura), and to provide a theoretical basis for the target treatment of the disease. In the period of December 2015, 27 children with HSP in the Provincial Hospital Affiliated to Shandong University were treated as experimental group, and 22 cases of healthy children in the same period were used as control group. Among them, the experimental group was divided into the acute period group and the recovery group after the treatment. All the children were in accordance with the European Union of European rheumatic disease and the European paediatric rheumatism. The diagnostic standard of EULAR/PReS allergic purpura was found in the healthy control group without the history of recent infection and the history of blood system and other system related diseases. The peripheral blood of children in the acute, convalescent and healthy controls of all the patients was extracted by enzyme linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR (Quantitative Real-time PCR) method. The serum levels of IL-33 and sST2 and the expression of mRNA were measured, and the serum levels of related factors IL-4, IL-5 and IL-6 were detected. The relationship between the changes of these factors and the occurrence of HSP, the development of HSP and its clinical significance were investigated. Results: the serum IL-33 level (365.5 soil 160.6pg/ml) in acute 1.HSP children was significantly higher than that of the IL-33 (186.7 + 101.5pg/ml) and the recovery period. The normal control group (175.9 + 92.8pg/ml) (175.9 + 92.8pg/ml) (P0.05), HSP children's recovery period compared with the normal control group, there was no significant difference in IL-33 level (P0.05) in the acute phase of.HSP in children with 35T2 (1788.6 + 523.8pg/ml), the recovery period 35T2 (1182.5 + 455.7pg/ml) and the healthy group of serum sST2 (1083.6 +) also increased, but the difference was not statistically significant Learning significance (P0.05). (see Table 2) the serum IL-4 (20.1 + 14.7pg/ml) in the acute phase of children with 2.HSP and the serum IL-4 (16.9 + 13.0pg/ml) in the healthy control group were all higher, the difference was statistically significant (0.05). There was no significant difference in the IL-4 level between the HSP recovery period and the healthy control group (P0.05).HSP children in the acute phase of serum IL-5 (18.7 + 3). .9pg/ml), compared with the recovery period (9.7 + 2.9pg/ml) and the healthy control group (9.1 + 3.2pg/ml), the difference was statistically significant (P0.05) the serum IL-6 level (208.7 + 31.3pg/ml) in children with.HSP was significantly higher than that in the recovery period (40.1 + 6.2pg/ml) and the normal control group (32.4 + 4.7pg /ml) (P0.05). There was no statistical significance (P0.05). (see Table 2) the serum sST2/IL-33 ratio (4.84 + 3.21) in the acute phase of 3.HSP children was significantly lower than that in the recovery period (6.81 + 3.57) and the healthy control group (6.77 se 3.84) (P0.05). There was no significant difference between the recovery period and the healthy control group sST2/IL-33 (P0.05). (see Figure 1) 4. real-time fluorescent quantitative PCR results confirmed that the acute stage IL-33 of HSP children was IL-33 The level of mRNA in the recovery period was increased (5.39 + 2.08) times, higher than that in the normal control group (5.47 + 1.97) times, the difference was statistically significant (P0.05). There was no significant difference in the level of IL-33 mRNA in the recovery period of HSP children and the healthy control group (P0.05) the sST2mRNA water level of the children in the acute phase of.HSP was higher (2.97 + 1.91) times than that of the normal control group (3.13, 3.13). The difference was statistically significant (P0.05) (P0.05) there was no significant difference in the level of sST2 mRNA in the recovery period and the healthy control group (P0.05). (see Figure 2) the ratio of sST2/IL-33 mRNA to the acute stage of children 5.HSP was significantly lower than that in the recovery period and the healthy control group (P0.05), and there was no significant difference between the restorer period and the healthy control group (P0.05). (see Figure 3) 1. (1.): 1. The levels of serum IL-33, IL-4, IL-5 and IL-6 in patients with acute phase HSP were significantly higher than those in the recovery period and normal control group of HSP patients. It was suggested that these four factors may be closely related to the occurrence and development of HSP, which may be closely related to the mild elevation of serum sST2 level in the acute phase of children with.2.HSP and the normal control group, but there is no statistical significance, but the study shows that sST2 is used as a lure. The combination of deceive receptor and IL-33 can not cause signal conduction, but hinders the transmission of IL-33/ST2 signal. It suggests that sST2 may be a protective factor in the acute phase of HSP.3.HSP children's sST2/IL-33 ratio in the recovery period and the normal control group, indicating that the imbalance of sST2/IL-33 in the HSP patients may be an important cause of the occurrence of HSP. Remodeling of sST2/IL-33 balance may be a new direction and strategy for the treatment of HSP.
【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】:R725.5
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