雾化吸入布地奈德对肺纤维化大鼠肺组织MMP-2、TIMP-2表达的影响  

The Effect of Inhaled Budesonide on the Expression MMP2 and TIMP-2 in Lung Tissues of Rats with Pulmonary Fibrosis

作　　者：张小波[1] 范贤明[1] 王文军[1] 湛晓琴[1] 曾鸣[1] 朱晨[1] 

机构地区：[1]泸州医学院附属医院呼吸内科,四川泸州646000

出　　处：《西南军医》2008年第4期12-15,共4页Journal of Military Surgeon in Southwest China

基　　金：四川省教育厅资助项目(05011);泸州医学院附属医院资助项目(06059)

摘　　要：目的探讨布地奈德雾化吸入对博莱霉素(BLM)致肺纤维化大鼠肺组织基质金属蛋白酶-2(MMP-2)及金属蛋白酶抑制剂-2(TIMP-2)表达的影响。方法Wistar大鼠45只,随机分成博莱霉素模型组(BLM组)、生理盐水空白对照组(NS组)和布地奈德干预组(Bud组)各15只,BLM组和Bud组气管内灌注博莱霉素诱导肺纤维化,NS组在相同条件下灌注生理盐水。气管内灌注药物后,第0~6天Bud组给予布地奈德雾化吸入,其余组在相同条件下给予生理盐水雾化吸入。各组分别于第7、142、8天随机处死5只,收集肺组织作切片、行HE及Masson染色,判断肺组织肺泡炎及肺纤维化程度;行免疫组化染色,检测MMP-2和TIMP-2在肺组织的表达水平。结果与NS组相比,Bud组第7、14、28天肺组织的肺泡炎和肺纤维化程度明显加重(P<0.5);与BLM组相比,Bud组第7、14天肺组织的肺泡炎程度明显减轻(P<0.05),第7、14、28天肺纤维化程度明显减轻(P<0.05);与NS组相比,BLM组第7、14、28天MMP-2和TIMP-2表达明显增加(P<0.5);与BLM组相比,Bud组第7、142、8天MMP-2和TIMP-2表达明显降低(P<0.05)。结论布地奈德雾化吸入可减轻BLM致肺纤维化大鼠的肺泡炎和肺纤维化程度,其干预机制可能为降低肺组织内MMP-2及TIMP-2的表达,并在一定程度上调整MMP-2/TIMP2的比值。Objective To investigate the effect of inhaled budesonide on the expression of matix metallopmteinases-2（ MMP-2 ） and tissue inhibitors of metalloproteinases -2 （TIMP-2） in lung tissues of rats with bleomycin - induced pulmonary fibrosis. Methods 45 Wistar rats were randomly divided into 3 groups： the bleomycin （BLM） group, the budesonide （Bud） group and the normal solution （ NS） group. Intratracheal perfusion of BLM was made to the Bud group and the BLM group to induce pulmonary fibrosis while perfusion of normal solution to the NS group in the same condition. From 0 to 6 days after perfusion, aerosol inhalation of Bud was given to the Bud group but normal saline to other groups in the same condition. On the 7th, 14th, and 28th day~, the rats were killed, 5 rats from each group each time, and the lung tissues were sectioned which were dyed by HE and Masson to determine the extent of alveolitis and pul- monary fibros^s, and then the expression levels of MMP-2 and TIMP-2 in lung tissues were detected. Results On the 7th, 14th, and 28th day, the extent of alveolitis and pulmonary fibrosis of the Bud group were much higher than those of the NS group （ P 〈 0.5） but much lower than those of the BLM group （0.05） ; on the 7th, 14th, and 28th day, theexpression levels of MMP-2 and TIMP-2 in the BLM group were much higher than those in the NS group （ P 〈 0.5） while the levels in the Bud group were much lower than those in the BLM group （ P 〈 0.05）. Conclusions The aerosol inhalation of budesonide can meliorate the extent of bleomycin - induced alveolitis and pulmonary fibrosis in lung tissues of the rats, the intervention mechanism is probably contributed to the reduction of the expression levels of MMP-2 and TIMP-2 in lung tissues and the regulation of the ratio of MMP-2 and TIMP-2 to some extent.

关 键 词：布地奈德 肺纤维化 博莱霉素 基质金属蛋白酶-2(MMP-2) 金属蛋白酶抑制剂-2(TIMP-2) 

分 类 号：R-33[医药卫生]