中文摘要：

目的：探讨mi R-449b在高迁移率族蛋白B1（HMGB1）刺激树突状细胞（DC）中的变化及其对DC免疫功能的影响。方法：分别以10、100、1 000 ng/ml剂量的HMGB1刺激小鼠脾脏来源的CD11c＋DC,于48后检测DC表面分子CD80、CD86、MHC-II及细胞内mi R-449b改变;流式细胞仪分析不同剂量HMGB1刺激对DC凋亡的影响。DC转染mi R-449b模拟物（mi R-449b）、抑制物（In-mi R-449b）及相应对照（mi R-NC、In-mi RNC）后,HMGB1（100 ng/ml）刺激48 h收取细胞,检测DC表面分子、凋亡改变以及与T细胞混合培养后T细胞增殖、分化功能的变化。结果：HMGB1刺激DC后,其表面分子随着剂量的增加表达上调,其中以100 ng/ml组上调最为明显,而大剂量（1 000 ng/ml）时表达有所下调;mi R-449b在48 h 100及1 000 ng/ml HMBG1组表达明显上调（P〈0.05）;随着HMGB1剂量的增加,DC在48 h凋亡逐渐增加（P〈0.05）。转染mi R-449b可上调其在细胞内表达,而抑制物可抑制其表达;上调mi R-449b后HMGB1（100 ng/ml）刺激48 h DC表面分子CD86表达显著上调（P〈0.05）、凋亡增加（P〈0.01）、对T细胞的共刺激增殖效应减弱、混合性淋巴细胞反应中IL-4水平增多（P〈0.01）、IFN-γ水平下降（P〈0.05）。结论：mi R-449b可负性调控HMGB1介导DC免疫功能及促进其凋亡,进而在机体免疫反应障碍过程中发挥调控作用。

英文摘要：

Objective： To investigate the changes in mi R-449 b in dendritic cells（DCs） stimulated by high mobility group box-1 protein（HMGB1） and its potential effect on DC-mediated immunity. Methods： CD11c＋ DCs isolated from mouse spleens were treated with different doses of HMGB1（10, 100, and 1000 ng/ml） for 48 hours, and then, the expressions of costimulatory molecules, including CD80, CD86, and MHC-II, and mi R-449 b in DCs were determined, and apoptosis of DCs stimulated by different doses of HMGB1 were analyzed with flow cytometry. After DCs were transfected with mi R-449 b mimics（mi R-449b）, negative control mimics（mi R-NC）, mi R-449 b inhibition（In-mi R-449b）, and negative control inhibition（In-mi R-NC）, DCs were challenged by HMGB1（100 ng/ml） for 48 hours. The expressions of co-stimulatory molecules on DC surface and cell apoptosis were analyzed. Moreover, the activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. Results： The co-stimulatory molecule expressions were markedly up-regulated after DCs were treated with HMGB1 for 48 hours, especially in 100 ng/ml HMGB1 stimulation group, on the other hand, they decreased after DCs were treated with 1000 ng/ml HMGB1. The expression of mi R-449 b in DCs was enhanced after being stimulated by 100 and 1000 ng/ml HMGB1 for 48 hours（P0.05）. The percentage of apoptosis was elevated with the increase in the dose of HMGB1 at 48 hours（P0.05）. The expression of mi R-449 b in DCs was up-regulated after mi R-449 b transfection and inhibited by In-mi R-449 b tranfection. Meanwhile, mi R-449 b transfection and 100 ng/ml HMGB1 stimulation（48 hours） could significantly up-regulate the expression levels of CD86（P0.05）, while apoptosis of DC was promoted, proliferative effect weakened（P0.01）, showing an increased level of IL-4 and the decreased level of IFN-γ.Conclusions： Mi R-449 b might negatively regulate the immune function of DC stimulated by HMGB1 and promote the ap