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[NLRP1在异基因造血干细胞移植后非感染性肺损伤中的作用]

[The function of NLRP1 in noninfectious pulmonary injury following allogeneic hematopoietic stem cell transplantation].

作者信息

Li M F, Li W, Ding L, Wu Y L, Liu L, Ju W, Qiao J L, Xu K L, Zeng L Y

机构信息

Department of Hematology, Xuzhou Medical University, Jiangsu Province Xuzhou 221002, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2017 Jul 14;38(7):607-611. doi: 10.3760/cma.j.issn.0253-2727.2017.07.011.

Abstract

To explore the function of NLRP1 in noninfectious pulmonary injury (nonIPI) after allogeneic stem cell transplantation (allo-HSCT) . In this study, we established the model of allo-HSCT with C57BL/6 and NLRP(-/-) mouse as recipients. Chimera rate was measured by flow cytometry. The HE staining was used to observe the pathology changes in the lungs. NLRP1 and relevant inflammatory proteins were measured by Western Blot. On the day 14 after allo-HSCT, the chimera rate was more than 96%, HSCs of donors had been successfully transplanted into recipients. HE staining showed that nonIPI occurred after allo-HSCT. The degrees of injuries reached the peak on day 21. In addition, the expressions of MPO, NLRP1, p20, Mature-IL-1β and Mature-IL-18 had same tends with the degrees of nonIPI. When we knocked out NLRP1 gene of recipients, the degrees of nonIPI reduced and the expressions of MPO, p20, Mature-IL-1β and Mature-IL-18 were less than in non-knockout group. allo-HSCT could cause nonIPI and high expressions of MPO, p20, IL-1β, IL-18, NLRP1. Knocking out NLRP1 gene could alleviate the degrees of nonIPI and reduce the expressions of relevant inflammatory proteins, indicating that NLRP1 might be one of factors contributed to nonIPI after allo-HSCT.

摘要

为探究NLRP1在异基因干细胞移植(allo-HSCT)后非感染性肺损伤(nonIPI)中的作用。在本研究中,我们以C57BL/6和NLRP(-/-)小鼠作为受体建立了allo-HSCT模型。通过流式细胞术检测嵌合率。采用苏木精-伊红(HE)染色观察肺部病理变化。通过蛋白质免疫印迹法检测NLRP1及相关炎症蛋白。allo-HSCT后第14天,嵌合率超过96%,供体造血干细胞已成功移植到受体中。HE染色显示allo-HSCT后发生了nonIPI。损伤程度在第21天达到峰值。此外,髓过氧化物酶(MPO)、NLRP1、p20、成熟白细胞介素-1β(Mature-IL-1β)和成熟白细胞介素-18(Mature-IL-18)的表达与nonIPI程度呈相同趋势。当敲除受体的NLRP1基因时,nonIPI程度降低,MPO、p20、Mature-IL-1β和Mature-IL-18的表达低于未敲除组。allo-HSCT可导致nonIPI以及MPO、p20、白细胞介素-1β、白细胞介素-18、NLRP1的高表达。敲除NLRP1基因可减轻nonIPI程度并降低相关炎症蛋白的表达,表明NLRP1可能是allo-HSCT后导致nonIPI的因素之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82c3/7342275/1a8213fdacd4/cjh-38-07-607-g001.jpg

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