本文選題：銀屑病　切入點(diǎn)：Notch　出處：《中國(guó)免疫學(xué)雜志》2017年07期 　論文類型：期刊論文

【摘要】：目的:探討Notch1信號(hào)通路對(duì)銀屑病模型小鼠Th17細(xì)胞分化和功能的調(diào)控作用。方法:以5%咪喹莫特外涂聯(lián)合α-2b干擾素腹腔注射的方法制備20只銀屑病模型小鼠,免疫磁珠分離小鼠脾臟CD4~+T淋巴細(xì)胞,流式細(xì)胞術(shù)檢測(cè)Th17細(xì)胞比例,實(shí)時(shí)熒光定量RT-PCR檢測(cè)Th17細(xì)胞特異性轉(zhuǎn)錄因子RORγt、效應(yīng)性細(xì)胞因子IL-17A、Notch1信號(hào)分子及其靶基因Hes-1的mRNA表達(dá)水平,并與10只對(duì)照組小鼠相比較。將銀屑病模型小鼠CD4~+T淋巴細(xì)胞分為未干預(yù)對(duì)照組和Notch1抑制劑組(γ-分泌酶抑制劑DAPT),檢測(cè)DAPT阻斷Notch1信號(hào)對(duì)銀屑病模型小鼠Notch1信號(hào)分子及Hes-1、Th17細(xì)胞比例、RORγt及IL-17A表達(dá)水平的影響。結(jié)果:銀屑病模型小鼠CD4~+T淋巴細(xì)胞中Th17細(xì)胞比例,RORγt、IL-17A、Notch1及Hes-1的mRNA表達(dá)水平均顯著高于對(duì)照小鼠[分別為(2.97±0.86)%比(0.65±0.11)%,t=15.083;(5.75±0.61)比(1.57±0.43),t=21.630;(7.83±0.97)比(1.63±0.31),t=25.348;(7.10±1.37)比(1.47±0.34),t=17.386;(7.30±1.15)比(1.67±0.48),t=18.840,P均0.01];與未干預(yù)對(duì)照組相比,銀屑病模型小鼠CD4~+T淋巴細(xì)胞各DAPT處理組中Notch1、Hes-1mRNA表達(dá)水平,Th17細(xì)胞比例、RORγt與IL-17A mRNA表達(dá)水平及培養(yǎng)上清液中IL-17A含量均明顯下降,組間比較差異具有統(tǒng)計(jì)學(xué)意義(F值分別為74.368、89.719、126.572、94.558、124.323和123.231,P均0.01),且隨DAPT濃度的增加呈劑量依賴性降低。結(jié)論:Notch1信號(hào)通路能夠調(diào)控銀屑病模型小鼠Th17細(xì)胞的分化和功能,對(duì)銀屑病的免疫靶向治療有潛在價(jià)值。
[Abstract]:Objective: to investigate the effects of Notch1 signaling pathway on the differentiation and function of Th17 cells in psoriatic model mice. Methods: twenty psoriatic model mice were induced by 5% imiquimod plus 偽 -2b interferon intraperitoneal injection. CD4 ~ T lymphocytes were isolated from mouse spleen by immunomagnetic beads, the proportion of Th17 cells was detected by flow cytometry, the mRNA expression levels of Th17 cell specific transcription factor ROR 緯 t, effector cytokine IL-17Atch1 signal molecule and its target gene Hes-1 were detected by real-time fluorescence quantitative RT-PCR. The CD4T lymphocytes of psoriatic model mice were divided into control group and Notch1 inhibitor group (Notch1 inhibitor DAPT). The effect of DAPT blocking Notch1 signal on Notch1 signal was detected in psoriatic model mice. The expression of ROR 緯 t and IL-17A in CD4 ~ T lymphocytes of psoriatic model mice was significantly higher than that in control mice (2.97 鹵0.86% vs 0.65 鹵0.113 鹵0.61), respectively. Results: the ratio of Th17 cells in CD4T lymphocytes of psoriatic mice was significantly higher than that in control mice (1.63 鹵0.31), 25.348 ~ (7.10 鹵1.3710) vs 1.47 鹵0.34 ~ (17.6)% vs 7.30 鹵1.15 (respectively). The expression of ROR 緯 t in psoriatic mice was higher than that in control mice (2.97 鹵0.86% vs 0.65 鹵0.11) and 1.57 鹵0.43 ~ T (21.6307.83 鹵0.97) vs 1.63 鹵0.31 (7.10 鹵1.3710) vs 1.47 鹵0.34 (7.30 鹵1.15)). Compared with the control group without intervention, there was no significant difference between the two groups (1.67 鹵0.48) and 18.840 (P 0.01). The expression level of Notch1Hes-1mRNA in CD4T lymphocytes of psoriatic mice and the ratio of Th17 cells to ROR 緯 t and IL-17A mRNA, and the content of IL-17A in culture supernatant were significantly decreased. The difference between the two groups was statistically significant (74.368,89.719) 126.57294.558 (124.323) and 123.231 (P) 0.01g, respectively, and decreased in a dose-dependent manner with the increase of DAPT concentration. Conclusion the DAPT signaling pathway can regulate the differentiation and function of Th17 cells in psoriatic model mice. Immune targeting therapy for psoriasis has potential value.
【作者單位】： 濱州醫(yī)學(xué)院附屬醫(yī)院;
【基金】：山東省醫(yī)藥衛(wèi)生科技發(fā)展計(jì)劃項(xiàng)目(2016WS0045)資助
【分類號(hào)】：R-332;R758.63

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