吸入性糖皮质激素对哮喘小鼠肺组织HMGB1、IL-1β表达的影响

摘要

目的 了解高迁移率族蛋白B1(HMGB1)及白介素-1β(IL-1β)在小鼠哮喘模型肺组织表达及分布以及吸入性糖皮质激素(ICS)对其影响.方法 SPF级雄性Balb/c小鼠随机分为对照组、哮喘组及布地奈德组,每组24只,分别于1、2、3、4周时每组各处死6只.RT-PCR法检测各组肺组织HMGB1 mRNA表达水平,免疫组化标记HMGB1、IL-1β在肺组织的分布,用Image-Pro Plus 图像分析系统分析IL-1β的灰度值.结果 HMGB1在对照组小鼠肺组织呈低表达,哮喘组第2周出现高峰,而布地奈德组第1周出现高峰,各组小鼠之间以及在第1 ～ 4周不同时间点之间,HMGB1表达的差异均有统计学意义(P均＜ 0.01);IL-1β的免疫组化标记在对照组小鼠肺组织中少,而哮喘组明显;布地奈德组则介于两者之间.肺组织IL-1β灰度值在哮喘组和布地奈德组小鼠中,从第1 ～ 4周,逐渐增加,各时间点差异有统计学意义(P均＜ 0.05);两组在不同时间点均低于对照组,差异有统计学意义(P均＜ 0.01);哮喘组在不同时间点又都低于布地奈德组,差异均有统计学意义(P ＜ 0.01).结论 HMGB1可能参与哮喘气道炎症,作用机制可能不同于IL-1β.%Objective To investigate the effect of inhaled glucocorticoid on the expression of high mobility group box 1 ( HMGB1 ) and interleukin-1 β (IL-1β ) in the lungs of asthmatic mice. Methods SPF male Balb/c mice were randomly divided into three groups of 24 mice each, asthmatic, budesonide and control. At the end of 1sl, 2nd, 3rd, and 4th week, 6 mice were sacrificed respectively. The expression of HMGB1 mRNA was detected in the lung tissues by reverse transcription PCR. The distribution of HMGB1 and IL-ip expression were marked with immunohistochem-istry. The IL-ip grey value was analysed by Image-Pro Plus analysis system. Results The expression of HMGB1 was lower in the lung tissues in control group. The expression of HMGB1 reached the peak at the end of 2nd week in inhaled glucocorticoid group and at the end of 1sl week in budesonide group. The expressions of HMGB1 were significantly different among three groups and at different time points ( all P < 0.01 ). The marker of immunohistochemistry in lung tissue was the least in normal saline control group, was the most in inhaled glucocorticoid group and was in the middle in budesoinde group. The IL-ip grey value was increased in inhaled glucocorticoid group and budesonide group from Is1 to 4* week. The difference was significant at different time points ( all P < 0.01 ). The IL-ip grey values were lower in inhaled glucocorticoid group and budesonide group than in control group at different time points, and were lower in inhaled glucocorticoid group than in budesonide group ( all P < 0.01 ). Conclusions HMGB1 may be involved in airway inflammation and its mechanism may be different from IL-1β.