雾化吸入布地奈德对肺纤维化大鼠肺组织MMP2、TIMP2表达影.doc

雾化吸入布地奈德对肺纤维化大鼠肺组织MMP2、TIMP2表达影 　 作者：张小波 ，范贤明，王文军，湛晓琴，曾鸣，朱晨 【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、14、28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（Plt;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(Plt;0.05)，第7、14、28天肺纤维化程度明显减轻(Plt;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（Plt;0.5）；与BLM组相比，Bud组第7、14、28天MMP2和TIMP2表达明显降低 (Plt;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。 【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） 　　The Effect of Inhaled Budesonide on the Expression MMP２ and TIMP２ in Lung Tissues of Rats with Pulmonary Fibrosis 　　Zhang Xiaobo, Fan Xianming, Wang Wenjun, Zhan Xiaoqin, Zeng Ming, Zhu Chen, the Attached Hospital to Luzhou Medical College, Luzhou, Sichuan Province 646000 　　ABSTRACT Objective To investigate the effect of inhaled budesonide on the expression of matix metalloproteinases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 pulmonary fibrosis, and then t