中文摘要：

目的探讨p38丝裂原活化蛋白激酶（p38 MAPK）对髓样相关蛋白8（MRP8）/髓样相关蛋白14（MRP14）诱导小鼠胚胎成纤维细胞凋亡的影响。方法制备MRP8、MRP14、MRP8/14备用。分别取p38^＋/＋和p38^-/-细胞,随机分为空白对照组、MRP8组、MRP14组、MRP8/14组。MRP8组、MRP14组、MRP8/14组分别加入50μg/m L MRP8、MRP14和MRP8/14。空白对照组加入等体积的DMEM培养液。各组干预24、48 h,采用MTT法检测p38^＋/＋和p38^-/-细胞活力。采用流式细胞术检测空白对照组及MRP8/14干预24、48 h组p38^＋/＋和p38^-/-细胞凋亡率。采用MTT法检测空白对照组、MRP8/14组以及TLR4受体抑制剂TAK242或RAGE中和抗体处理的MRP8/14（分别设为MRP8/14＋TAK242组、MRP8/14＋RAGE组）干预24 h p38^＋/＋细胞活力。采用MTT法和流式细胞术检测空白对照组、MRP8/14组以及p38激酶抑制剂SB203580处理的MRP8/14（设为MRP8/14＋SB203580组）干预24 h p38^＋/＋细胞活力和凋亡率。采用Western blotting法检测MRP8/14干预0、1、2、4、6、8 h p38^＋/＋细胞p38 MAPK磷酸化。结果 MRP8组、MRP14组、MRP8/14组干预24、48 h p38^＋/＋、p38^-/-细胞活力均低于空白对照组（P均〈0.05）,但无论MRP8/14组干预24 h还是48 h,p38^-/-细胞活力明显高于p38^＋/＋细胞（P均〈0.05）。MRP8/14干预24、48 h组p38^＋/＋细胞凋亡率均高于空白对照组,且MRP8/14干预48 h组细胞凋亡率更高（P均〈0.05）;而MRP8/14干预24、48 h组p38^-/-细胞凋亡率均未见明显变化（P均〉0.05）。MRP8/14组、MRP8/14＋RAGE组干预24 h p38^＋/＋细胞活力低于空白对照组、MRP8/14＋TAK242组干预24 h（P均〈0.05）。MRP8/14＋SB203580组干预24 h p38^＋/＋细胞活力较MRP8/14组干预24 h明显升高,细胞凋亡率较MRP8/14组干预24 h明显降低（P均〈0.05）。MRP8/14干预2、4、6 h p38^＋/＋细胞p38 MAPK磷酸化水平明显高于干预0、1、8 h（P均〈0.05）。结论 p38 MAPK能促进MRP8/14诱导?

英文摘要：

Objective To explore the role of p38 MAPK on the apoptosis of mouse embryo fibroblasts induced by myeloid-related protein 8（ MRP8）/myeloid-related protein 14（ MRP14）. Methods MTT assay was performed to detect the cell viability of p38^＋/＋and p38^-/-cells in the control group and groups in which cells were treated with 50 μg/m L MRP8,MRP14,and MRP8/14 for 24 h and 48 h; flow cytometry was applied to detect the apoptosis rate of p38^＋/＋and p38^-/-cells in the control group and groups in which cells were treated with 50 μg/m L MRP8/14 for 24 h and 48 h; MTT assay was performed to detect the cell viability of p38^＋/＋cells in the control group,MRP8/14 group,MRP8/14 ＋ TAK242（ TLR4 inhibitor） group and MRP8/14 ＋ RAGE neutralized antibody group for 24 h; MTT and flow cytometry were used to analyze the cell viability and the apoptosis rate of p38^＋/＋cells in the control group,MRP8/14 group,MRP8/14 ＋SB203580（ p38 MAPK inhibitor） group for 24 h; Western blotting was used to detect the phosphorylation changes of p38 MAPK in p38^＋/＋cells treated with MRP8/14 for 0,1,2,4,6,and 8 h,respectively. Results The cell viability of p38^＋/＋and p38^-/-cells in the groups treated with MRP8,MRP14,and MRP8/14 for 24 h and 48 h was lower than that of the control group（ P〈0. 05）. At the same time,the cell viability of p38^-/-cells was significantly higher than that of p38^＋/＋cells in the MRP8/14 group at 24 and 48 h（ P〈0. 05）.The apoptosis rate of p38^＋/＋cells in the MRP8/14 group at 24 and 48 h was higher than that of the control group,especially at 48 h（ all P〈0. 05）. However,the apoptosis rate of p38^-/-cells did not change after MRP8/14 treatment for 24 and 48 h. The cell viability of p38^＋/＋cells in the MRP8/14 group and MRP8/14 ＋ RAGE neutralized antibody group was lower than that in the control group and MRP8/14 ＋ TAK242 group（ P〈0. 05）. The cell viability of p38^＋/＋cells in the MRP8/14 ＋ SB203580 group was higher than that of the MRP8/14 alo