肺癌雾化吸入化疗的肺脏病理学研究

目的评估雾化吸入化疗的安全性及探讨肺损伤修复的机理。方法将紫杉醇3mg／kg、顺铂5nag／kg、5-FU2．5～10mg／kg、奥沙利铂2mg／kg雾化液通过呼吸机经口气管插管直接注入大鼠肺内。取肺脏常规HE染色观察肺的病理学变化，免疫组化染色检测腱糖蛋白-C（Tenascin—C）表达，明胶酶谱法检测基质金属蛋白酶（MMP-2、9）的活性。结果吸入紫杉醇可导致气管黏膜上皮部分增生,管周组织水肿，肺组织的肺泡壁增厚，大量中性粒细胞及淋巴细胞浸润，管壁增厚。肺泡有融合，但未见明显纤维化改变。顺铂、5-FU、奥沙利铂吸入后有程度很轻的相似表现，但未消失。Tenascin—C高表达于雾化后早期及后期仍有肺损伤时，MMP-9表达偏重于早期而MMP-2更多表达于后期。结论吸入＞3mg／kg紫杉醇可导致较严重肺损伤，吸入临床剂量的顺铂、5-FU及奥沙利铂比较安全，MMP-2与MMP-9可能在肺损伤修复过程中各有不同作用。

Pathological study of lung tissue in aerosolized chemotherapy

[Objective] To investigate the safety of aerosolized chemotherapy and the mechanism of lung remodeling. [Methods] The aerosol administration of PTX 3 mg/kg, DDP 5 mg/kg, 5-FU 2.5 - 10 mg/kg, oxaliplatin 2 mg/kg was carried out with tracheal intubation and mechanical aeration,immunohistochemistry was performed to evaluate the expression of tenascin-C,and gelatin enzymography was done to check the activity of matrix metalloproteinases-2.9. [Results] Histopathologic analysis revealed that lung tissues after PTX 3 mg/kg inhalation showed an intravascular neutrophil agglomerate ,perivascular/peribronchial damage ,parenchyma edema and thickening of alveolar wall. The extent of tissue lesions were significantly reduced but not abrogated in DDP or 5-FU or Oxaliplatin group. The expression of TN-C was significant immediately after inhalation and still higher at 4th week late when remodeling was remarkable. MMP-9 was more active at 1st week after inhalation than at 4th week and MMP-2 was contrary. [Conclusion] Inhalation of PTX more than 3mg/kg may lead to significant damage of lung tissue, and it seems more safer to inhalation DDP, 5-FU and oxaliplatin on present concentration. MMP-2 and MMP-9 may play different role at early and late pathologic remodeling of lung tissue after aerosolized chemotherapy.