高迁移率族蛋白1在内毒素急性肺损伤大鼠肺泡巨噬细胞吞噬功能改变中的作用

目的探讨高迁移率族蛋白1（HMGB1）在内毒素急性肺损伤大鼠肺泡巨噬细胞吞噬功能改变中的作用。方法脂多糖（LPS）注射复制大鼠急性肺损伤模型，在LPS致伤后不同时相点（有或无正丁酸钠SB干预时）获取肺组织及肺泡巨噬细胞（AM）。RT—PCR检测肺组织HMGB1 mRNA表达，应用鸡红细胞吞噬实验检测AM的吞噬功能，并对二者做平行比较。结果与对照组比较，LPS致伤后6、12、24h时相点AM吞噬率及吞噬指数明显降低；SB干预组AM吞噬功能于24h时相点出现较明显下降。与LPS组比较，6～12h时相点AM吞噬功能无明显降低，差异有统计学意义（P〈0．01）；LPS致伤后6～24h肺组织HMGB1 mRNA表达明显增高。正丁酸钠（SB）处理组动物肺组织于伤后6～12h肺组织HMGB1 mRNA表达均显著抑制，与LPS组比较，差异有显著性意义（P〈0．05）；相关性分析显示，肺泡巨噬细胞吞噬率及吞噬指数与肺组织HMGB1表达水平呈显著负相关。结论HMGB1高表达可能参与AM吞噬功能改变；AM吞噬功能减低可能是HMGB1参与急性肺损伤发生、发展的机制之一。

HMGB1 effects on changes in phagocytosis of alveolar macrophages in LPS-induced acute lung injury in rats

Objective To explore HMGB1 effects on changes in phagocytosis of alveolar macrophages in LPS-induced acute lung injury in rats.Methods LPS-induced acute lung injury rat model was developed by LPS infusion.At different time-points after LPS challenge in the presence or absence of SB,the rat tissue sample and alveolar macrophages were collected.RT-PCR was applied to examine rat lung tissue HMGB1 mRNA expression level.AM phagocytosis was detected by using chicken RBC phagocytosis assay.Comparative analysis was conducted to show the correlation between HMGB1 mRNA expression and AM phagocytosis.Results At 6h,12h,24h time point,as compared with that of normal control,the injuried rat AM phagocytosis ratio and phagocytosis index decreased significantly.By contrast,in SB group,AM phagocytosis ratio and phagocytosis index decreased significantly at 24h time point as compared with that of normal control,while at 6h,12h time point,the decrease was no significantly difference as compared with LPS group(P<0.01).The injuried rat lung tissue HMGB1 mRNA expression was upregulated after LPS exposure 6-24h,SB intervention significantly ameliorated the upregulation.The relative analysis showed a significant negative correlative relationship between AM phagocytosis changes and HMGB1 expression in rat lung tissue.Conclusion High expression of HMGB1 may be involved in AM phagocytosis changes.AM phagocytosis ability decrease may be one of mechanisms of pathogenesis and development of ALI.