雾化吸入布地奈德对肺纤维化大鼠肺组织MMP2、

　　【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（MMP2）及金属蛋白酶抑制剂2（TIMP2）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MMP2和TIMP2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MMP2和TIMP2表达明显增加（P<0.5）；与BLM组相比，Bud组第7、14、28天MMP2和TIMP2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MMP2及TIMP2的表达，并在一定程度上调整MMP2/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（MMP2）；金属蛋白酶抑制剂2（TIMP2）

　　The Effect of Inhaled Budesonide on the Expression MMP玻 and TIMP玻 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玻玻∕MP玻玻 and tissue inhibitors of metalloproteinases 玻 (TIMP玻) 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 the expression levels of MMP玻 and TIMP玻 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, the expression levels of MMP玻 and TIMP玻 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玻 and TIMP玻 in lung tissues and the regulation of the ratio of MMP玻 and TIMP玻 to some extent.

　　KEYWORDS    budesonide  pulmonary fibrosis       bleomycin   matix metalloproteinases玻玻∕MP玻玻  metalloproteinases 玻 (TIMP玻)

　　肺间质纤维化是许多慢性肺部疾病的终末病理过程，其发病率在全球呈上升趋势，其实质就是某些病理因素诱发肺损伤持续进行，继而导致细胞外基质（extracellular matrix ,ECM）代谢紊乱，某些细胞外基质成份在肺泡和间质内沉积，以及纤维组织过度修复造成肺组织结构紊乱。启动和调节肺损伤和持续过度修复的信号传导过程目前仍不清楚。近年来研究表明，基质金属蛋白酶（matrix metalloproteinases,MMPs）及其组织抑制剂（tissue inhibitors of metalloproteinases,TIMPs）在肺损伤和修复，以及肺纤维化的形成过程中起重要的调节作用。本实验采用博莱霉素(B1eomycin，BLM)对大鼠单次气管内灌注的方法，复制出大鼠肺纤维化模型，通过该模型了解布地奈德雾化吸入对肺组织中MMP2及TIMP2表达的影响，初步探讨其干预肺纤维化的作用机制。

　　1  材料与方法