【摘要】： 第一部分胚胎骨髓來源的間充質(zhì)干細(xì)胞對人T細(xì)胞免疫調(diào)節(jié)作用的研究 目的:研究胚胎骨髓來源的間充質(zhì)干細(xì)胞(FBM-MSCs)對人T細(xì)胞的免疫調(diào)節(jié)作用。 方法:在FBM-MSCs與正常人來源的外周血單個核細(xì)胞(PBMCs)的共培養(yǎng)體系中,進(jìn)行FBM-MSCs對PBMCs的增殖實驗,分別從實時定量PCR,ELISA,FCM等方面觀察FBM-MSCs對人Th17,Th1和Tregs細(xì)胞的調(diào)節(jié)作用。 結(jié)果:①在共培養(yǎng)體系中,FBM-MSCs可明顯抑制人PBMCs的增殖(p＜0.05);②相對于PBMCs單獨(dú)培養(yǎng)組,FBM-MSCs共培養(yǎng)組CD3+CD8-細(xì)胞比例上調(diào)(p＜0.05);③MSCs共培養(yǎng)組IL-17mRNA表達(dá)水平,上清IL-17水平和Th17細(xì)胞的數(shù)量明顯升高(p＜0.05);④MSCs共培養(yǎng)組IFN-γmRNA表達(dá)水平和上清IFN-γ的蛋白水平明顯減低(p＜0.05),同時,Th1和Tc1細(xì)胞數(shù)量也降低(p＜0.05);⑤FBM-MSCs可上調(diào)Foxp3 mRNA的表達(dá)水平(p＜0.05);⑥FBM-MSCs可上調(diào)IL-6 mRNA的水平(p＜0.05);⑦FBM-MSCs對IL-23的表達(dá)水平無明顯影響(p＞0.05)。 結(jié)論:FBM-MSCs可促進(jìn)人Th17和Tregs細(xì)胞的增殖,下調(diào)產(chǎn)IFN-γ的T細(xì)胞的產(chǎn)量。FBM-MSCs可能通過上調(diào)IL-6,而不是IL-23的表達(dá)而促進(jìn)Th17細(xì)胞的增殖。 第二部分干擾素治療肝炎病毒相關(guān)性血小板減少癥 目的:評價干擾素(IFN-α)對肝炎病毒相關(guān)性血小板減少癥患者的療效。 方法:對20例肝炎病毒相關(guān)性血小板減少癥患者進(jìn)行IFN-α治療,IFN-α具體 用法:3MU,皮下注射,一周兩次,至少2月。 結(jié)果:20例患者中男性14例,女性6例,中位年齡36.5歲(7～50歲)。HBV陽性15例,HCV陽性4例,HBV和HCV同時陽性1例。所有患者均以血小板減少為首發(fā)表現(xiàn),沒有肝硬化、門靜脈高壓或脾臟明顯增大的證據(jù)。9例患者獲得完全反應(yīng)(CR),6例部分反應(yīng)(PR),2例次要反應(yīng)(MR),CR率45%,總有效率85%,血小板反應(yīng)持久。應(yīng)用IFN-α治療沒有嚴(yán)重的不良反應(yīng)。 結(jié)論:IFN-α是治療肝炎病毒相關(guān)性血小板減少癥切實有效的方法。
[Abstract]:The first part of the study on the immunomodulatory effect of mesenchymal stem cells derived from embryonic bone marrow on human T cells objective: to study the immunomodulatory effect of mesenchymal stem cells (FBM-MSCs) derived from embryonic bone marrow on human T cells. Methods: in the co-culture system of FBM-MSCs and (PBMCs) of peripheral blood mononuclear cells (PBMC) derived from normal people, the proliferation of FBM-MSCs to PBMCs was carried out, and the effect of FBM-MSCs on human Th17,Th1 and Tregs cells was observed from the aspects of real-time quantitative PCR,ELISA,FCM and so on. Results in the co-culture system, FBM-MSCs significantly inhibited the proliferation of human PBMCs (p < 0. 05). Compared with PBMCs alone, the proportion of CD3 CD8- cells increased (p < 0. 05) and the expression level of IL-17mRNA was up-regulated in FBM-MSCs co-cultured group (p < 0. 05). The expression level of IFN- 緯 mRNA and the protein level of IFN- 緯 in supernatant were significantly decreased (p < 0. 05), and the number of Th1 and Tc1 cells were also decreased (p < 0. 05). 5FBM-MSCs could upregulate the surface of Foxp3 mRNA. (P < 0. 05) 6FBM-MSCs upregulated the level of IL-6 mRNA (p < 0. 05). 7FBM-MSCs had no significant effect on the expression of IL-23 (p > 0. 05). Conclusion: FBM-MSCs can promote the proliferation of human Th17 and Tregs cells, and down-regulate the production of IFN- 緯 -producing T cells. FBM-MSCs may promote the proliferation of Th17 cells by up-regulating the expression of IL-6, rather than IL-23. Part two: interferon in the treatment of hepatitis virus associated thrombocytopenia objective: to evaluate the efficacy of interferon (IFN- 偽) in patients with hepatitis virus associated thrombocytopenia. Methods: 20 patients with hepatitis virus associated thrombocytopenia were treated with IFN- 偽. Results among the 20 patients, 14 were male and 6 were female. The median age was 36.5 years old (750 years) .15 cases were positive for HCV and 4 cases were positive for both HBV and HCV. Thrombocytopenia was the first manifestation in all patients. There was no evidence of cirrhosis, portal hypertension or splenic enlargement in 9 patients. Complete response (CR) was obtained in 6 cases, partial response (PR) in 2 cases, (MR) CR rate in 2 cases, total effective rate 85%, platelet reaction lasting. There was no serious adverse reaction in the treatment of IFN- 偽. ConclusionTwo-IFN- 偽 is an effective and effective method for the treatment of hepatitis virus associated thrombocytopenia.
【學(xué)位授予單位】：中國協(xié)和醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R392

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1 曹蘭;王曦;謝俊麗;;HCV和HIV感染并發(fā)血小板減少性紫癜1例[J];臨床血液學(xué)雜志;2006年03期

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