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過敏性紫癜患兒血清中IL-33及可溶性受體的表達(dá)研究

發(fā)布時(shí)間:2018-05-19 17:40

  本文選題:過敏性紫癜 + 白介素33; 參考:《山東大學(xué)》2017年碩士論文


【摘要】:目的:檢測白介素33(interleukin-33,IL-33)、IL-33可溶性ST2受體(soluble ST2,sST2)、IL-4、IL-5及IL-6在過敏性紫癜(Henoch-Schonlein purpura,HSP)患兒外周血中的表達(dá)水平,探討其與HSP發(fā)生發(fā)展的內(nèi)在聯(lián)系,為疾病的靶向治療提供理論依據(jù)。方法:選取2015年8月至2015年12月期間在山東大學(xué)附屬省立醫(yī)院就診的27例HSP患兒作為實(shí)驗(yàn)組,22例本院同期健康體檢兒童作為對照組,其中,實(shí)驗(yàn)組又分為初診時(shí)的急性期組和治療后的恢復(fù)期組。所有患兒均符合2006年歐洲抗風(fēng)濕病聯(lián)盟和歐洲兒科風(fēng)濕病學(xué)會(huì)(EULAR/PReS)過敏性紫瘢的診斷標(biāo)準(zhǔn),健康對照組均無近期感染史及血液系統(tǒng)和其他系統(tǒng)相關(guān)疾病史。抽取全部患者急性期、恢復(fù)期及健康對照組兒兒童外周血,采用酶聯(lián)免疫吸附法(ELISA)和實(shí)時(shí)熒光定量PCR(Quantitative Real-time PCR)法檢測其IL-33及sST2血清表達(dá)水平及mRNA表達(dá)量,并同時(shí)檢測相關(guān)因子IL-4、IL-5及IL-6的血清水平,探討上述因子的變化與HSP發(fā)生、發(fā)展的關(guān)系及其臨床意義。結(jié)果:1.HSP患兒急性期血清IL-33水平(365.5土160.6pg/ml)明顯高于恢復(fù)期IL-33(186.7± 101.5pg/ml)及正常對照組IL-33(175.9±92.8pg/ml)(P0.05),HSP患兒恢復(fù)期與正常對照組相比,IL-33水平差異無統(tǒng)計(jì)學(xué)意義(P0.05)。HSP患兒急性期血清35T2(1788.6±523.8pg/ml),較恢復(fù)期35T2(1182.5±455.7pg/ml)及健康對照組血清sST2(1083.6±489.6pg/m])亦有升高,但差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。(見表2)2.HSP患兒急性期血清IL-4(20.1±14.7pg/ml)較恢復(fù)期(16.3±12.1pg/ml)及健康對照組血清IL-4(16.9±13.0pg/ml)均升高,差異有統(tǒng)計(jì)學(xué)意義(尸0.05),HSP恢復(fù)期與健康對照組IL-4水平無顯著差異(P0.05)。HSP患兒急性期血清IL-5水平為(18.7±3.9pg/ml),較恢復(fù)期(9.7±2.9pg/ml)及健康對照組(9.1±3.2pg/ml)升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。HSP患兒急性期血清IL-6水平(208.7±31.3pg/ml)明顯高于恢復(fù)期(40.1 ±6.2pg/ml)及正常對照組(32.4±4.7pg/ml)(P0.05),HSP患兒恢復(fù)期與正常對照組相比,IL-6水平差異無統(tǒng)計(jì)學(xué)意義(P0.05)。(見表2)3.HSP患兒急性期血清sST2/IL-33比值(4.84±3.21)明顯低于恢復(fù)期(6.81±3.57)及健康對照組(6.77士3.84)(P0.05),恢復(fù)期與健康對照組sST2/IL-33差異無統(tǒng)計(jì)學(xué)意義(P0.05)。(見圖1)4.實(shí)時(shí)熒光定量PCR結(jié)果證實(shí),HSP患兒急性期IL-33 mRNA水平較恢復(fù)期升高(5.39±2.08)倍,較正常對照組升高(5.47± 1.97)倍,差異均有統(tǒng)計(jì)學(xué)意義(P0.05),HSP患兒恢復(fù)期與健康對照組IL-33 mRNA水平差異無統(tǒng)計(jì)學(xué)意義(P0.05)。HSP患兒急性期sST2mRNA水平較恢復(fù)期升高(2.97±1.91)倍,較正常對照組升高(3.13±2.01)倍,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。HSP患兒恢復(fù)期與健康對照組sST2 mRNA水平差異無統(tǒng)計(jì)學(xué)意義(P0.05)。(見圖2)5.HSP患兒急性期sST2/IL-33 mRNA比值較恢復(fù)期及健康對照組明顯降低(P0.05),恢復(fù)期與健康對照組無明顯差異(P0.05)。(見圖3)結(jié)論:1.急性期HSP患者血清IL-33、IL-4、IL-5及IL-6水平明顯高于HSP患者恢復(fù)期及正常對照組,提示這四種因子與HSP的發(fā)生發(fā)展可能存在密切關(guān)系。2.HSP患兒急性期血清sST2水平較恢復(fù)期及正常對照組輕度升高,但無統(tǒng)計(jì)學(xué)意義,而研究表明sST2作為誘騙受體與IL-33結(jié)合不能引起信號(hào)傳導(dǎo),而是阻礙IL-33/ST2信號(hào)傳導(dǎo),提示sST2可能作為一種保護(hù)性因素參與HSP。3.HSP患兒急性期sST2/IL-33比值較恢復(fù)期及正常對照組明顯降低,說明HSP患者體內(nèi)sST2/IL-33水平失衡,可能是導(dǎo)致HSP發(fā)生的重要原因,重塑sST2/IL-33平衡可能是治療HSP的一個(gè)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.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R725.5

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