本文選題：異基因造血干細(xì)胞移植 + 急性移植物抗宿主病��； 參考：《中國(guó)實(shí)驗(yàn)血液學(xué)雜志》2017年01期

【摘要】：目的:探討阻斷Caspase1對(duì)小鼠急性移植物抗宿主病(aGVHD)的影響及其作用機(jī)制。方法:用Caspase1特異性抑制劑Ac-YVAD-CMK阻斷Caspase1活化。實(shí)驗(yàn)小鼠分為異基因造血干細(xì)胞移植聯(lián)合脾細(xì)胞輸注(TS組,n=12)、TS+低劑量Caspase1抑制劑(TS+C低組,n=16)和TS+高劑量Caspase1抑制劑(TS+C高組,n=19)共3組。檢測(cè)各組小鼠體重變化,觀察小鼠GVHD臨床評(píng)分;應(yīng)用HE染色觀察GVHD靶器官的(肝臟、肺、結(jié)腸、皮膚)病理學(xué)改變,并作病理評(píng)分;流式細(xì)胞術(shù)檢測(cè)外周血中Th1、Th2和Th17細(xì)胞的比例;酶聯(lián)免疫吸附測(cè)定法(ELISA)檢測(cè)各組小鼠血漿中IL-1β、IFN-γ、IL-1α、IL-18水平。結(jié)果:AC-YVAD-CMK能減輕小鼠aGVHD:與TS組相比,TS+C低組和TS+C高組的aGVHD嚴(yán)重程度明顯減輕(P0.05);通過(guò)檢測(cè)各組小鼠外周血Th細(xì)胞亞群發(fā)現(xiàn),與TS組相比,TS+C低組和TS+C高組的Th1細(xì)胞比例明顯減少(P0.05),Th2和Th17細(xì)胞比例明顯增多(P0.05);ELISA檢測(cè)小鼠外周血IL-1β、IFN-γ、IL-18和IL-1α顯示,TS+C高組和TS+C低組與TS組相比,上述4種炎癥因子水平均明顯降低(P0.05)。結(jié)論:Ac-YVAD-CMK通過(guò)抑制Caspase1活化,減少炎癥性介質(zhì)釋放,從而減輕aGVH臨床癥狀和病理?yè)p傷。
[Abstract]:Aim: to investigate the effect and mechanism of blocking Caspase1 on acute graft-versus-host disease (GV HDD) in mice. Methods: Caspase1 specific inhibitor Ac-YVAD-CMK was used to block the activation of Caspase1. Mice were divided into three groups: allogeneic hematopoietic stem cell transplantation (HSCT) combined with splenic cell infusion (TS group), low dose Caspase1 inhibitor (TS-C) and TS high-dose Caspase1 inhibitor (TS-C). The changes of body weight and the clinical score of GVHD were observed, and the pathological changes of the target organs of GVHD (liver, lung, colon, skin) were observed by HE staining. The ratio of Th1 Th 2 and Th17 cells in peripheral blood was detected by flow cytometry, and the plasma levels of IL-1 尾 -IFN- 緯 -IL-1 偽 and IL-18 were detected by Elisa. Results the weight AC-YVAD-CMK could alleviate the aGVHD: compared with TS group, the severity of aGVHD in TS C low group and TS C high group was significantly reduced, and the Th cell subsets in peripheral blood of each group were detected. Compared with TS group, the proportion of Th1 cells in low TS C group and high TS C group was significantly decreased. The proportion of P0.05Th 2 and Th17 cells was significantly increased. The detection of IL-1 尾 -IFN- 緯 IL-18 and IL-1 偽 in peripheral blood of mice by Elisa showed that the ratio of IL-1 尾 -IFN- 緯 IL-18 and IL-1 偽 in the high TS C group and the low TS C group was significantly higher than that in the TS group. The levels of the above four inflammatory factors were significantly decreased. ConclusionAc-YVAD-CMK can reduce the release of inflammatory mediators by inhibiting the activation of Caspase1, thereby alleviating the clinical symptoms and pathological injury of aGVH.
【作者單位】： 徐州醫(yī)科大學(xué)血液病研究所;徐州醫(yī)科大學(xué)附屬醫(yī)院血液科;
【基金】：國(guó)家自然科學(xué)基金(81300441) 江蘇省”六大人才高峰”資助項(xiàng)目(2013-WSN-080) 江蘇省自然科學(xué)基金(BK20161177) 中國(guó)博士后基金(2016M590507)
【分類號(hào)】：R457.7

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本文編號(hào)：1980114