本文選題：過敏性紫癜　切入點(diǎn)：紫癜性腎炎　出處：《南昌大學(xué)》2012年碩士論文

【摘要】：目的： 用Roche NimbleGen人基因表達(dá)譜芯片技術(shù)篩選過敏性紫癜(HenochSchonlein purpura，HSP)患兒疾病發(fā)生及腎損傷相關(guān)基因，以進(jìn)一步從分子水平更全面、系統(tǒng)地分析兒童HSP發(fā)生發(fā)展及腎損傷發(fā)生機(jī)制。 方法： 利用Roche NimbleGen人基因表達(dá)譜芯片（約含有45033個基因）,分別檢測單純過敏性紫癜組外周血（HSP）、紫癜性腎炎組外周血(HSPN)、健康對照組外周血（C）的基因表達(dá)譜，用相關(guān)生物信息學(xué)分析方法對不同實驗組間基因表達(dá)譜進(jìn)行差異分析，最后應(yīng)用實時定量PCR技術(shù)對部分差異表達(dá)基因進(jìn)行驗證。 結(jié)果： 1、單純過敏性紫癜組與對照組間：共有1064條差異表達(dá)基因，其中2倍以上差異基因225條，2.5倍以上38條，3倍以上5條；其中225條2倍以上差異基因中146條表達(dá)上調(diào)，79條表達(dá)下調(diào)。紫癜性腎炎組與單純過敏性紫癜組：共有830條差異表達(dá)基因，其中2倍以上差異基因283條，2.5倍以上118條，3倍以上51條；其中283條2倍以上差異基因中180條表達(dá)上調(diào)，103條表達(dá)下調(diào)。 2、隨機(jī)選取其中3條差異基因進(jìn)行Real．time PCR驗證，其結(jié)果與基因芯片篩查結(jié)果一致，結(jié)果充分證實表達(dá)譜芯片差異表達(dá)基因結(jié)果的可靠性。 3、對單純過敏性紫癜組與對照組2倍以上差異基因進(jìn)行GO生物學(xué)過程分析發(fā)現(xiàn)，已知功能分類的共119條，主要涉及：轉(zhuǎn)錄/翻譯、物質(zhì)合成/代謝過程和信號轉(zhuǎn)導(dǎo)/通路相關(guān)基因，其次為分化/發(fā)育、免疫/炎癥和凋亡/抗凋亡相關(guān)基因；而在紫癜性腎炎組與單純過敏性紫癜組2倍以上差異基因中，我們發(fā)現(xiàn)已知功能分類的有201條，主要涉及：物質(zhì)合成/代謝過程相關(guān)基因，其次為轉(zhuǎn)錄/翻譯、免疫/炎癥、信號轉(zhuǎn)導(dǎo)/通路、分化/發(fā)育和細(xì)胞周期。 4、初步篩選出免疫炎癥/細(xì)胞黏附/信號轉(zhuǎn)導(dǎo)通路相關(guān)基因AIF1、LAMC2、BCAM、CD209、MFAP4、ELMOD3、SCUBE1、ADAM33、RET、CLEC7A、MASP2、TAPS、AOAH、MGST2、PSMA3、SP100，代謝/凋亡相關(guān)基因MUC3B、MUC1、HSD11B1、MTHFS、TNFAIP8及未知基因BM88、CEACAM3等可能在HSP發(fā)病中起重要作用，，同樣也篩選出免疫炎癥/信號轉(zhuǎn)導(dǎo)通路相關(guān)基因KRT18、GRB10、VEGFB、HSP90AB1、HSPD1、F12、TGFBR2、TGM2、UBE2L6、CTSS、PXDN、GBP2、HLA-DRB1、HLA-DMA、HLA-DPA1，代謝/分化發(fā)育/凋亡相關(guān)基因SORD、HSPE1、ARG2、HSP90AA2、PRAME、TNFAIP2、MMP19、ZFP36L1，細(xì)胞黏附相關(guān)基因CLDN4及未知基因CKMT1B等可能與HSP腎臟損傷的發(fā)生密切相關(guān)。 結(jié)論： 1、首次用快速高通量的表達(dá)譜芯片篩選出過敏性紫癜及紫癜性腎炎相關(guān)基因。 2、初步篩選出(AIF1、BCAM、CLEC7A、CD209、AOAH、MAPS2等)可能導(dǎo)致HSP發(fā)病的易感基因，進(jìn)一步證實了免疫炎癥、細(xì)胞黏附相關(guān)基因的表達(dá)異常可能在HSP發(fā)病過程中起到了主導(dǎo)作用，同時也發(fā)現(xiàn)了一些可能導(dǎo)致HSP發(fā)生的代謝/凋亡相關(guān)基因（如MUC3B、HSD11B1、MTHFS、TNFAIP8等）及未知基因。 3、研究不僅證實了在HSP腎損傷過程中可能起重要作用的已被認(rèn)識的基因如VEGFB、HLA-DRB1，也首次發(fā)現(xiàn)了一些以往在HSPN發(fā)病過程中未曾報道的已知基因（如SORD、ARG2、ZFP36L1、TGM2、KRT18等）以及未知基因。 4、針對這些基因的深入研究，將有助于更全面、系統(tǒng)地揭示過敏性紫癜的分子機(jī)制。
[Abstract]:Purpose :

The pathogenesis of HSP and the pathogenesis of renal injury in children with Henoch Schonlein purpura ( HSP ) were screened by using the Roche NileGen gene expression profiling chip technique .

Method :

The gene expression profiles of peripheral blood ( HSP ) , Henoch - Schonlein purpura nephritis ( HSPN ) and healthy control group ( C ) were detected by using the Roche NileGen gene expression profiling chip ( about 45033 genes ) . The gene expression profiles of different experimental groups were analyzed by means of bioinformatics analysis . Finally , the partial differential expression gene was verified by real - time quantitative PCR .

Results :

1 . There were a total of 1064 differential expression genes , among which more than 2 times the difference gene was 225 , 2.5 times more than 38 , 3 times more than 5 ;
Among them , more than 225 of these genes were up - regulated and 79 were down - regulated . There were 830 differentially expressed genes , among them , there were 830 differentially expressed genes , more than 2 times the difference gene 283 , 2.5 - fold or more than 118 , and more than 3 times 51 ;
Of these , the expression of 180 in 283 2 - fold difference gene was up - regulated and 103 expression was down - regulated .

2 . Three different genes were randomly selected for Real . time PCR . The results were consistent with the results of gene chip screening .

3 . The analysis of GO biological process of 2 - fold difference gene in Henoch - Henoch - Schonlein purpura group and control group showed that 119 of the known functions were involved : transcription / translation , substance synthesis / metabolic process and signal transduction / pathway - related gene , followed by differentiation / development , immune / inflammation and apoptosis / anti - apoptosis related genes ;
Among the 2 - fold difference genes in the Henoch - Schonlein purpura nephritis group and the simple allergic purpura group , we found that there were 201 known functional classes , mainly involved in gene synthesis / metabolic process - related genes , followed by transcription / translation , immune / inflammation , signal transduction / pathway , differentiation / development and cell cycle .

4 . The related genes AIF1 , LAMC2 , BCAM , CD209 , MFAP4 , ELMOD3 , SCUBE1 , CD209 , MAP4 , ELMOD3 , SCUBE1 , TAPS , AOAH , MGST2 , PSMA3 , TAPS , AOAH , MGST2 , PSMA3 , SP100 , TNFAIP8 and unknown genes BM88 , CEACAM3 and so on may play an important role in the pathogenesis of HSP . MMP - 19 , ZFP36L1 , cell adhesion - related gene CLDN4 and unknown gene CKMT1B may be closely related to HSP renal injury .

Conclusion :

1 . The genes associated with Henoch - Schonlein purpura and Henoch - Schonlein purpura nephritis were screened for the first time with a fast high - throughput expression profiling chip .

2 . Preliminary screening ( AIF1 , BCAM , CLEC7A , CD209 , AOAH , MAPS2 , etc . ) may lead to the susceptibility gene of HSP , further confirming the immune inflammation , the abnormal expression of cell adhesion - related genes may play a leading role in the pathogenesis of HSP , and some genes related to the metabolism / apoptosis of HSP ( such as MUC3B , HSD 11B1 , HFS , TNFAIP8 , etc . ) and unknown genes are also found .

3 . The research not only confirmed that the known genes , such as VEGFB , HLA - DRB1 , which may play an important role in the course of HSP kidney injury , also first discovered some known genes ( such as SORD , ARG2 , ZFP36L1 , TGM2 , KRT18 , etc . ) which have not been reported in the pathogenesis of HSP .

4 . In - depth study of these genes will help more comprehensively and systematically reveal the molecular mechanism of Henoch - Schonlein purpura .

【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R725.5

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