Caspase1抑制剂Ac-YVAD-CMK在防治小鼠急性移植物抗宿主病中的作用

发布时间：2018-06-05 02:48

  本文选题：异基因造血干细胞移植 + 急性移植物抗宿主病　； 参考：《中国实验血液学杂志》2017年01期

【摘要】：目的:探讨阻断Caspase1对小鼠急性移植物抗宿主病(aGVHD)的影响及其作用机制。方法:用Caspase1特异性抑制剂Ac-YVAD-CMK阻断Caspase1活化。实验小鼠分为异基因造血干细胞移植联合脾细胞输注(TS组,n=12)、TS+低剂量Caspase1抑制剂(TS+C低组,n=16)和TS+高剂量Caspase1抑制剂(TS+C高组,n=19)共3组。检测各组小鼠体重变化,观察小鼠GVHD临床评分;应用HE染色观察GVHD靶器官的(肝脏、肺、结肠、皮肤)病理学改变,并作病理评分;流式细胞术检测外周血中Th1、Th2和Th17细胞的比例;酶联免疫吸附测定法(ELISA)检测各组小鼠血浆中IL-1β、IFN-γ、IL-1α、IL-18水平。结果:AC-YVAD-CMK能减轻小鼠aGVHD:与TS组相比,TS+C低组和TS+C高组的aGVHD严重程度明显减轻(P0.05);通过检测各组小鼠外周血Th细胞亚群发现,与TS组相比,TS+C低组和TS+C高组的Th1细胞比例明显减少(P0.05),Th2和Th17细胞比例明显增多(P0.05);ELISA检测小鼠外周血IL-1β、IFN-γ、IL-18和IL-1α显示,TS+C高组和TS+C低组与TS组相比,上述4种炎症因子水平均明显降低(P0.05)。结论:Ac-YVAD-CMK通过抑制Caspase1活化,减少炎症性介质释放,从而减轻aGVH临床症状和病理损伤。
[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- 纬 -IL-1 伪 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- 纬 IL-18 and IL-1 伪 in peripheral blood of mice by Elisa showed that the ratio of IL-1 尾 -IFN- 纬 IL-18 and IL-1 伪 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.
【作者单位】： 徐州医科大学血液病研究所;徐州医科大学附属医院血液科;
【基金】：国家自然科学基金(81300441) 江苏省”六大人才高峰”资助项目(2013-WSN-080) 江苏省自然科学基金(BK20161177) 中国博士后基金(2016M590507)
【分类号】：R457.7

【相似文献】

相关期刊论文 前1条

1 袁淑芳;姜涛;胡兰英;孙丽华;郑嵘炅;张跃新;;骨髓间充质干细胞移植对急性肝衰竭大鼠Caspase1和IL-18表达的影响[J];世界华人消化杂志;2014年06期

，

本文编号：1980114