本文關(guān)鍵詞： 阿司匹林 牙齦 間充質(zhì)干細(xì)胞 免疫調(diào)節(jié)　出處：《北京大學(xué)學(xué)報(醫(yī)學(xué)版)》2017年05期 　論文類型：期刊論文

【摘要】：目的:檢測乙酰水楊酸(acetylsalicylic acid,ASA)對牙齦干細(xì)胞(mesenchymal stem cells derived from gingiva,GMSCs)免疫調(diào)節(jié)功能的影響,初步探索乙酰水楊酸對干細(xì)胞治療免疫相關(guān)疾病療效的提高作用及機(jī)制。方法:通過流式細(xì)胞儀分析ASA對GMSCs干細(xì)胞表面標(biāo)志分子CD146、CD105、CD90、CD34和CD45的影響,通過Brd U摻入法以及MTT細(xì)胞實驗檢測GMSCs增殖率。建立GMSCs與T細(xì)胞體外共培養(yǎng)系統(tǒng),通過流式細(xì)胞儀分析細(xì)胞凋亡并用酶聯(lián)免疫吸附測定法(enzyme linked immunosorbent assay,ELISA)檢測相關(guān)炎癥因子。進(jìn)一步建立硫酸葡聚糖(dextran sulfate sodium,DSS)誘導(dǎo)性小鼠腸炎模型,通過追蹤小鼠體重等臨床表現(xiàn)以及結(jié)腸病理組織切片,研究GMSCs注射對DSS誘導(dǎo)腸炎的治療作用,以研究ASA對GMSCs免疫調(diào)節(jié)功能的促進(jìn)作用,并進(jìn)一步探索其分子機(jī)制。結(jié)果:ASA促進(jìn)GMSCs增殖并調(diào)高CD146及CD105等干細(xì)胞表面標(biāo)記分子在GMSCs的表達(dá)。GMSCs與T細(xì)胞共培養(yǎng)中,GMSCs誘導(dǎo)T細(xì)胞凋亡,ASA可以增強(qiáng)GMSCs誘導(dǎo)T細(xì)胞凋亡,同時抑制T細(xì)胞分泌炎癥因子干擾素γ和腫瘤壞死因子α。GMSCs注射對DSS誘導(dǎo)性小鼠腸炎具有治療作用,表現(xiàn)為小鼠體重下降減緩、腸炎臨床指數(shù)降低、結(jié)腸組織切片HE染色顯示炎性細(xì)胞浸潤減少及病理指數(shù)降低,ASA可以促進(jìn)GMSCs注射治療小鼠腸炎療效。分子機(jī)制上,ASA通過調(diào)高Fas/Fas L信號通路Fas L的表達(dá)促進(jìn)GMSCs誘導(dǎo)T細(xì)胞凋亡。結(jié)論:ASA增強(qiáng)GMSCs免疫調(diào)節(jié)功能,促進(jìn)GMSCs對小鼠誘導(dǎo)性腸炎的治療作用。
[Abstract]:Objective: to investigate the effect of acetylsalicylic acidicylic acid (ASAA) on the immunomodulatory function of mesenchymal stem cells derived from gingivaan (GMSCs) of gingival stem cells. Objective: to explore the effect and mechanism of acetylsalicylic acid on the treatment of immune-related diseases by stem cells. Methods: the effects of ASA on CD146T CD105 CD90 CD90 CD34 and CD45 were analyzed by flow cytometry. The proliferation rate of GMSCs was detected by Brd U incorporation and MTT cell experiment. The co-culture system of GMSCs and T cells was established in vitro. Apoptosis was analyzed by flow cytometry (FCM) and the inflammatory factors were detected by enzyme linked immunosorbent assayama Elisa. The model of mouse enteritis induced by dextran sulfate dextran sulfate (DSS) was further established. The therapeutic effect of GMSCs injection on DSS induced enteritis was studied by tracking the clinical manifestations such as weight of mice and pathological sections of colon in order to study the effect of ASA on the immunomodulatory function of GMSCs. Results WASA promoted the proliferation of GMSCs and increased the expression of CD146 and CD105 on the surface of stem cells. In the co-culture of GMSCs and T cells, GMSCs induced T cell apoptosis. ASA could enhance GMSCs induced T cell apoptosis. At the same time, inhibiting T cell secretion of inflammatory factor interferon 緯 and tumor necrosis factor 偽. GMSCs injection had therapeutic effect on DSS induced enteritis in mice, which showed that the weight loss and clinical index of enteritis in mice were slow and the clinical index of enteritis was decreased. The HE staining of colonic sections showed that the decrease of inflammatory cell infiltration and the decrease of pathological index could promote the therapeutic effect of GMSCs injection in the treatment of mouse enteritis. The molecular mechanism was that ASA promoted GMSCs induced T by increasing the expression of Fas L in Fas/Fas L signaling pathway. Conclusion: ACA can enhance the immune regulation of GMSCs. To promote the therapeutic effect of GMSCs on induced enteritis in mice.
【作者單位】： 北京大學(xué)口腔醫(yī)學(xué)院·口腔醫(yī)院正畸科口腔數(shù)字化醫(yī)療技術(shù)和材料國家工程實驗室口腔數(shù)字醫(yī)學(xué)北京市重點實驗室;
【基金】：國家國際科技合作專項基金(2015DFB30040) 國家自然科學(xué)基金(81600865、81470717)資助~~
【分類號】：R392

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