1-磷酸鞘氨醇在慢性阻塞性肺疾病大鼠肺部炎症作用的研究

Role of Sphingosine 1-Phosphate in Pulmonary Inflammation of Chronic Obstructive Pulmonary Disease Rats

目的:观察1-磷酸鞘氨醇(S1P)在慢性阻塞性肺疾病(COPD)大鼠肺组织的表达,了解S1P在COPD大鼠炎症中的作用。方法:熏香烟与气管注射内毒素相结合法建立COPD大鼠动物模型,造模8周后,测定肺功能确定造模成功,获取支气管肺泡灌洗液(BALF),计数灌洗液中炎症细胞数量,ELISA法检测IL-6、TNF-α的水平;处死动物取肺组织行HE染色,Western Blot方法检测肺组织组蛋白去乙酰化酶(HDAC)、S1P蛋白的表达。结果:BALF上清液中炎性细胞总数、中性粒细胞数、淋巴细胞数、单核/巨噬细胞数比值较对照组增高,IL-6、TNF-α水平较对照组升高,均有统计学差异(P<0.05);COPD组肺功能检测第0.1秒用力呼气容积(FEV0.1)、FEV0.1/FVC、PEF均高于对照组,有统计学差异(P<0.05);COPD组大鼠肺组织S1P的蛋白表达水平升高,HDAC表达降低,与对照组比较有统计学意义(P<0.05)。结论:S1P可能参与了COPD肺部炎症的进程。

Objective：To observe the role of sphingosine 1-phosphate（S1P）in inflammation of chronic obstructive pulmonary disease（COPD）.Methods：The models of COPD rats were made by smoked cigarettes and intratracheal injection of endotoxin,lung functions of rats were measured to ensure the model success afer 8weeks.At the same time,lung bronchial alveolar lavage（BAL）was gained to measure the inflammatory cells which was tested by ELISA number and IL-6,TNF- αlevels of COPD rat.Lung tissues of COPD rats were extracted to measure the protein expression of histone deacetylase（HDAC）and S1 Pby Western blot.Results：Compared with control group,the total number of inflammatory cells,neutrophil,lymphocyte count,monocyte/macrophage increased in COPD rats（P〈0.05）.IL-6and TNF-αin BAL level were higher in COPD than in control group（P〈0.05）.Higher expression of S1 Pand lower expression of HDAC were found in COPD rats than in control group（P〈0.05）.Conclusion：S1P may be involved in the inflammation of COPD rats.