噬血细胞综合征患儿外周血单核细胞Toll样受体2、3、4表达水平的研究

发布时间：2018-03-06 17:03

本文选题：噬血细胞综合征　切入点：Toll样受体　出处：《遵义医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的:本研究通过分析噬血细胞综合征患儿外周血单核细胞Toll样受体2、3、4和下游信号传导分子、效应分子的表达改变,旨在进一步研究噬血细胞综合征发病机制,为其诊断、治疗提供理论依据。方法:采用流式细胞术对18例初发噬血细胞综合征患儿及18例正常同龄健康儿童的外周血单核细胞TLR2、3、4蛋白表达水平进行检测,同时采用实时荧光定量PCR方法对TLR传导通路中My D88、TRAF6、IRAK4、TRAM、TRIF、TBK1、IRF3等信号分子m RNA表达进行检测,比较两组间差异;并运用ELISA方法比较两组间血浆中IL-1β,IFN-α,INF-β,TFN-α表达水平的差异。结果:1)HLH组外周血单核细胞TLR2、3、4表达比例均明显高于健康对照组(P均0.05)。2)TLR信号传导通路中各信号分子m RNA检测结果:HLH组My D88、TRAF6、IRAK4、TRAM、TRIF、TBK1、IRF3较健康对照组升高。其中My D88、TRAF6、IRAK4三者m RNA表达较健康对照组升高,P均0.05,差异有统计学意义;TRIF、TBK1、IRF3的m RNA较正常对照组略有升高,但无统计学差异(P0.05);HLH组TRAM分子m RNA表达水平低于健康对照组,P0.05,具有统计学差异。3)HLH组血浆细胞因子IL-1β,IFN-γ及TNF-α水平较健康对照组明显升高(P0.05),IFNF-α水平在HLH组虽较正常对照组有所增高但其差异无统计学意义(其P0.05)。结论:1)TLR2、3、4的大量表达,提示TLR2、3、4在HLH的发病过程中起重要作用。2)HLH的发生过程可能由于内源性/外源性配体诱导TLR2/4-My D88依赖性通路信号传导及效应分子IRAK4等大量活化,以及同时存在而在TRIF依赖性通路中TRAM,TRIF等分子的失活或表达受到抑制所致。3)HLH之所以存在“炎症因子风暴”可能正是因为My D88依赖信号通路的活化,炎性细胞因子高表达,同时TRIF信号通路异常,导致I型干扰素释放受到影响,清除病毒能力下降;因子分泌失衡,使得病毒持续刺激,使体内炎性因子(IL-1,TNF-α,IFN-γ)大量堆积导致。
[Abstract]:Objective: to study the expression changes of Toll receptor 2m3O4 and downstream signal transduction molecules and effector molecules in peripheral blood monocytes of children with hemophagocytic syndrome, in order to further study the pathogenesis and diagnosis of hemophagocytic syndrome. Methods: flow cytometry was used to detect the expression of TLR2O3O4 protein in peripheral blood monocytes of 18 children with primary hemophagocytic syndrome and 18 normal children of the same age. At the same time, the expression of m RNA was detected by real-time fluorescence quantitative PCR method in the TLR transduction pathway, such as my D88TBK1 / IRF3 signal molecule TRAF6 / IRAK4 / TramTBK1 / IRF3, and the difference between the two groups was compared. ELISA method was used to compare the expression level of IL-1 尾 -IFN- 伪 -INF- 尾 -INF- 尾 -TFN- 伪 in plasma between the two groups. Results the expression rate of TLR2O3TN- 伪 in peripheral blood monocytes in the group of 1: 1 HLH was significantly higher than that in the healthy control group (P 0.05). The results of m RNA detection of each signal molecule in the signal transduction pathway of TLR were obtained. The m RNA expression of my D888-TRAF6TRAF6 / IRAK4TRAMTRIFTBK1 / IRF3 was significantly higher than that of the healthy control group (P < 0.05), and the m RNA of TBK1 IRF3 was slightly higher than that of the normal control group (P < 0.05). However, there was no statistical difference in the expression of m RNA of TRAM in P0.05HLH group as compared with that in the normal control group. There was a significant difference in the levels of plasma cytokine IL-1 尾 -IFN- 纬 and TNF- 伪 between the HLH group and the normal control group, although the level of P0.05FNF- 伪 in the HLH group was significantly higher than that in the normal control group. Conclusion the high expression of TLR2TLR2O3O4 was found at 1: 1, but the difference was not statistically significant (P0.05). The results suggest that TLR2O3HLH may play an important role in the pathogenesis of HLH. The endogenous / exogenous ligand induces TLR2/4-My D88-dependent signal transduction and a large number of activation of effector molecule IRAK4. The existence of "inflammatory factor storm" caused by the simultaneous inactivation or inhibition of TRAMN TRIF and other molecules in the TRIF dependent pathway may be due to the activation of my D88 dependent signaling pathway and the high expression of inflammatory cytokines. At the same time, the abnormal TRIF signaling pathway affected the release of interferon type I and decreased the ability to clear the virus, and the imbalance of factor secretion caused the continuous stimulation of the virus and the accumulation of the inflammatory factor IL-1TNF- 伪 (IFN- 纬) in the body.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.5

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