【摘要】 目的探讨p38蛋白激酶在脂多糖(LPS)刺激肺泡巨噬细胞激活机制中的作用。方法分离培养大鼠肺泡巨噬细胞,设正常对照组、LPS刺激组、SB203580干预组(SB203580+LPS组)。分别采用免疫组织化学和原位分子杂交方法检测p38蛋白质及其mRNA的表达,用放射免疫分析法检测细胞培养上清TNF-αI、L-8的含量。结果LPS刺激肺泡巨噬细胞p38胞核染色阳性细胞百分比、胞浆p38mRNA的表达以及培养上清TNF-αI、L-8含量显著升高,分别为正常对照组的5.75倍、1.44倍、3.57倍和3.22倍;加入SB203580预处理后,上述指标均较LPS刺激组显著下降,较正常对照组稍高,但差异无显著性。肺泡巨噬细胞p38蛋白质胞核染色阳性细胞百分比及其mRNA的表达与培养上清TNF-αI、L-8含量均呈显著正相关。结论LPS刺激肺泡巨噬细胞释放炎性细胞因子可能是通过p38蛋白激酶介导的,抑制p38的活性可能成为治疗炎症反应的一条新途径。更多还原

【Abstract】 ObjectiveTo investigate the role of p38 protein kinase in the activation of alveolar macrophages(AMs) induced by lipopolysaccharide(LPS).MethodsAMs isolated and purified from nor-mal rats which were divided into three groups: control group,LPS-stimulated group and SB203580+ LPS group.The expression of p38 protein and mRNA were observed by immunocytochemical staining and in situ hybridization staining respectively.The concentrations of TNF-αand IL-8 in supernatants were measured by radioimmunoassay.ResultsThe percentages of positive cells of p38 protein,p38 mR-NA and the levels of TNF-αand IL-8 in LPS-stimulated group were significantly higher than those in control group(P<0.01).By using SB203580 before LPS stimulated,the above indexes were signifi-cantly reduced compared with those in LPS-stimulated group(P<0.01),and still higher but not signif-icantly compared with those in control group(P>0.05).There were good positive correlation between the percentage of positive cells of p38 protein,p38 mRNA and the concentrations of TNF-αand IL-8 in supernatant(r=0.751,0.635,0.712 and 0.845,P<0.01).ConclusionThese results indicate that p38 protein kinase plays an important role in the LPS-activated signaling pathway that regulates TNF-αand IL-8 production by AMs.Inhibiting the activity of p38 protein kinase may be useful to treat the inflam-matory diseases.更多还原