中文摘要：

目的探讨腺苷酸环化酶抑制剂（SQ22536）和激动剂（Forskolin）在脂多糖（LPS）诱导的急性肺损伤（acute lung injury,ALI）中的作用。方法 ICR小鼠随机分为生理盐水组（N组）、模型组（L组）、地塞米松组（D组）、SQ22536组（SQ组）和Forskolin组（F组）,气道内滴入LPS制备ALI模型。6 h后观察肺组织病理改变,测定肺泡灌洗液（BALF）中白细胞、中性粒细胞和白蛋白含量,检测肺组织中髓过氧化物酶（MPO）、肿瘤坏死因子-α（TNF-α）、白介素-1β（IL（-1）β）、白介素-6（IL-6）和c AMP含量。结果 Forskolin可明显改善肺组织病理变化,降低BALF中白细胞、中性粒细胞和蛋白含量,MPO活性和TNF-α含量明显降低,c AMP含量升高;SQ22536与M组相比差异均无显著性。结论 Forskolin对ALI的保护机制可能与升高c AMP水平、抑制中性粒细胞黏附和趋化及降低TNF-α等相关炎症因子含量有关。

英文摘要：

Aim To explore the effect of adenylate cyclase（ AC） antagonists SQ22536 and agonist forskolin on acute lung injury induced by lipopolysaccharide.Methods ICR mice were randomly divided into normal saline control group（ N group）, model group（ group L）,dexamethasone group（ group D）,AC antagonists s（ group SQ） and AC agonist group（ group F）. The ALI mouse model was induced by instilling intratracheally with LPS（ 2 mg·kg~（-1））,and 6 h later,the lung tissue and alveolar lavage fluid（ BALF） were harvested,pathological changes in lung were observed,white blood cell and neutrophil,albumin content inBALF and myeloperoxidase（ MPO） activity of lung tissue homogenate were determined,and tumor necrosis factor α（ TNF-α）,interleukin-1β（ IL-1β）,interleukin 6（ IL-6） and c AMP content in lung homogenates were detected by ELISA. Results Compared with normal saline group,a large number of neutrophils infiltrated around the pulmonary vessel and airway 6 h after LPS intratracheal instillation in model group. White blood cells and neutrophils and protein content increased in BALF; MPO activity and c AMP levels increased in lung tissues. In the lung tissue TNF-α and IL-6,IL-1β content increased,compared with model group. Forskolin could improve the pathological changes of lung tissue,reduce the total number of leukocytes,number of neutrophils and protein content in BALF,and reduce MPO activity and TNF-α content in lung tissue,at the same time it increased the c AMP content; SQ22536 had no significant effect when compared with model group. Conclusion AC agonistshave protective effects on LPS-induced acute lung injury in mice,and the mechanism may be related to elevating c AMP levels,inhibiting neutrophil adhesion and chemotaxis and reducing inflammatory factor levels.