卡托普利对大鼠肺纤维化及肺上皮细胞凋亡的影响

Effects of Captopril on Pulmonary Fibrosis and Apoptosis of Pulmonary Epithelial Cells in Rats

目的:探讨卡托普利对实验大鼠肺纤维化的干预作用及可能的作用机制。方法:60只SD大鼠经气管内灌注博来霉素诱导肺纤维化,随机分为博莱霉素(BLM)组、卡托普利(CAP1)和CAP2组,分别给予生理盐水、卡托普利50mg·kg-1·d-1和60mg·kg-1·d-1灌胃,并于1,7,14,28d各处死5只,取肺组织行嗜伊红染色组织学观察及羟脯氨酸测定,评价肺泡炎和肺纤维化程度、免疫组织化学及电镜检查评价肺上皮细胞凋亡程度。结果:与BLM组比较CAP1组和CAP2组肺泡炎及肺纤维化程度明显减轻(P<0.05),气道上皮细胞和肺泡上皮细胞凋亡程度显著改善(P<0.01),CAP1和CAP2两组间无显著性差异。结论:卡托普利能有效抑制博来霉素诱导的肺纤维化,其可能的抗纤维化机制之一是抑制肺上皮细胞凋亡。

Objective: To investigate the effects of captopril on the development of pulmonary fibrosis and the possible underlying mechanisms. Methods:Pulmonary fibrosis was induced with intratracheal infusion of blemycin in 60 rats. These rats were divided into BLM group which was treated with saline, CAP 1 and CAP2 groups which were administered with captopril at doses of 50mg/kg and 60mg/kg per day respectively. On 1,7,14,and 28 days after bleomycin treatment,5 rats in each group were killed and the lungs were harvested. The degree of pulmonary fibrosis was evaluated by histology and detection of hydroxyproline. The apoptosis in lung epithelial cells was detected using in situ terminal Deoxynucleotidyl dUTP nick-end labeling(TUNEL) and electron microscopy. Results: The degree of pulmonary fibrosis decreased significantly and apoptosis of lung epithelial cells was markedly improved in CAP group as compared with BLM group(P<0.05). Conclusion: Captopril can attenuate bleomycin-induced pulmonary fibrosis and its possible mechanism is inhibiting apoptosis of lung epithelial cells.