双哌达莫和腺苷对小鼠肺纤维化的干预作用

目的　通过腺苷 (ADO)受体拮抗剂 茶碱 (TH) ,探讨ADO、双哌达莫 (DPM)对小鼠肺间质纤维化过程的干预作用。方法　 1 0 0只小鼠经气道注入博莱霉素 (BLM ,8.5mg/kg)制备肺纤维化动物模型 ,随机分成BLM、DPM、ADO和TH 4组 ,分别给予生理盐水 (1 0 0 μl/d)、DPM (50mg·kg- 1 ·d- 1 )、ADO(50mg·kg- 1 ·d- 1 )、DPM和TH (50mg·kg- 1 ·d- 1 ) ,共 7天 ,第 4～ 30天内处死动物 ,观察肺超微结构与病理变化。结果　BLM组肺泡上皮细胞坏死多 ,内皮伸出许多长棘突呈现肺组织缺氧 ,1 0天后间质出现大量成纤维细胞 ,因胶原增加伴炎症细胞浸润导致肺泡隔增宽 ;第 2 0天后DPM和ADO两组与BLM组比较 ,坏死肺泡上皮细胞少 ,第 4～ 30天活跃的肺泡巨噬细胞 (AM)数量增多 ,胞质内含大量溶酶体与吞饮小泡 ,第 30天塌陷肺泡与成纤维细胞均减少 ;TH组坏死肺泡上皮细胞很多 ,毛细血管闭锁、因肺组织缺血 ,间质内浸润的单核细胞发育成巨噬细胞延迟 ,成纤维细胞很少。结论　BLM能损伤肺泡上皮细胞致缺氧是成纤维细胞大量增生的重要因素之一 ,DPM与ADO通过改善微循环 ,促进AM发育和肺泡腔重建 ,以抑制成纤维细胞的增生

The effect of dipyridamole and adenosine on pulmonary fibrosis in mice

Objective To evaluate the effect of dipyridamole (DPM) and adenosine(ADO) on interstitial pulmonary fibrosis in mice. Methods 100 mice injected with Bleomycin (BLM,8.5 mg/kg) by intratracheal were divided into a control group and groups treated by DPM, ADO, DPM and theophyline (TH). Pulmonary pathology from day 4 to day 30 observations was studied by light and electron microscope. Results Alveolar epithelial cell necrosis, lung tissue lesions by hypoxia and interstitial fibrosis were found in the BLM group after day 10. The necrotic epithelial cell, fibroblast proliferation, and the hypoxia induced tissue damage were less prominent, and the number and phagocytic function of macrophages were increased in the DPM and ADO treated groups. In the TH treated group, necrotic epithelial cells increased, the lung tissue was ischemic, and the differentiation of monocytes in pulmonary interstitia was slower. Conclusion DPM and ADO can inhibit fibroblast proliferation by improving microcirculation and promoting macrophage development and alveolar space reconstruction.