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息肉狀脈絡膜血管病變血清藥物靶向因子的初步篩選

發(fā)布時間:2018-08-06 15:17
【摘要】:目的利用蛋白芯片技術篩選息肉狀脈絡膜(PCV)血清差異性蛋白,以便尋找PCV的早期診斷標志物和藥物治療新靶點,為進一步探討PCV發(fā)病機制提供依據(jù)。方法1.用AAH-BLG-507蛋白芯片(含507種功能蛋白)檢測隨機抽取的1例陰性對照組、1例AMD患者及2例PCV患者血清中相應蛋白的表達水平,分析差異性表達蛋白。2.根據(jù)AAH-BLG-507蛋白芯片結果,選取相關細胞因子和趨化因子構建成含34種因子的多因子檢測試劑盒(即液相芯片),檢測65例PCV患者(男性42例,女性23例;年齡分布在49歲到81歲之間)和70例陰性對照組(男性40例,女性30例;年齡分布在53歲到78歲之間)血清中相關34種因子的表達,篩選有差異性表達的因子。結果1.入組的PCV患者平均年齡(65.43±8.57)歲,與對照組相比無顯著差異(P=0.070.05)。兩組性別構成比較,結果顯示無顯著差異(P0.05),認為兩組患者年齡和性別匹配。2.AAH-BLG-507蛋白芯片檢測結果分析顯示,有79種蛋白表達有差異,其中58種在PCV患者血清中呈上調趨勢,21種呈下調趨勢。分析表達差異性蛋白之間關系,結果顯示主要分為細胞因子、趨化因子、胞外基質蛋白/基質金屬蛋白酶、生長因子及新生血管相關因子及其受體4大類。3.多因子檢測試劑盒結果顯示,選取的34種因子中有10種有統(tǒng)計學差異(P0.05)其中8種因子及其在PCV血清中對應的濃度:Eotaxin(52.618±24.954)pg/mL,IL-1RA(289.232±146.678)pg/m L;IL-1β(0.481±0.279)pg/mL、IL-4(2.069±1.050)pg/mL、IL-5(0.169±0.111)pg/mL、IL-13(0.424±0.122)pg/mL、IL-22(4.730±3.790)pg/m L、GM-CSF(1.542±0.752)pg/mL,明顯高于其在對照組血清濃度,即這8種因子在PCV患者血清中呈上調趨勢(P值分別為0.003、0.007、0.009、0.002、0.040、0.003、0.003、0.003均0.05)。而另外2種因子在PCV患者血清中濃度IL-7(2.929±2.749)pg/mL、SDF-1α(347.141±101.243)pg/m L明顯低于對照組,即呈下調趨勢(P值分別為0.003和0.008均0.05)。結論1.蛋白芯片技術是一種快速、簡便的高通量蛋白質組研究方法,為PCV研究提供了新的研究策略。2.PCV的發(fā)病可能與患者血清中Eotaxin、IL-1RA、GM-CSF、IL-1β、IL-4、IL-5、IL-13、IL-22表達上調和IL-7、SDF-1α表達下調相關。3.篩選出的PCV相關的差異蛋白,將可能作為PCV患者的診斷分子標志物和藥物治療靶向因子。
[Abstract]:Objective to screen serum differential proteins of polypoid choroidal (PCV) by using protein chip technique in order to search for early diagnostic markers and new targets of drug therapy for PCV and to provide evidence for further study of pathogenesis of PCV. Method 1. The expression levels of the corresponding proteins in the serum of 1 AMD patient and 2 PCV patients were detected by AAH-BLG-507 protein chip (including 507 functional proteins), and the differentially expressed protein. 2 was analyzed. According to the results of AAH-BLG-507 protein chip, 34 cytokines and chemokines were selected to construct a multifactor detection kit (liquid chip) containing 34 factors. 65 patients with PCV were detected (42 males and 23 females). Age ranged from 49 to 81 years old) and 70 cases of negative control group (male 40, female 30; age between 53 and 78 years old) had 34 related factors. Result 1. The mean age of the patients with PCV was (65.43 鹵8.57) years old, which was not significantly different from that of the control group (P0.070.05). The results showed that there was no significant difference between the two groups (P0.05). It was considered that the age and sex matched. 2.AAH-BLG-507 protein chip analysis showed that there were 79 protein expression differences between the two groups. 58 of them were up-regulated in serum of PCV patients and 21 were down-regulated. The expression of differentially expressed proteins was analyzed. The results showed that they were divided into four categories: cytokines, chemokines, extracellular matrix proteins / matrix metalloproteinases, growth factors and neovascularization related factors and their receptors. 澶氬洜瀛愭嫻嬭瘯鍓傜洅緇撴灉鏄劇ず,閫夊彇鐨,

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