摘要
目的探讨吸入丙酸氟替卡松对博莱霉素（BLM）致肺纤维化大鼠肺组织基质金属蛋白酶-2（MMP-2）及基质金属蛋白酶组织抑制物-1（TI MP-1）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）和丙酸氟替卡松干预组（FP组）,各15只。BLM组和FP组气管内灌注BLM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BLM后,第0-6天FP组给予丙酸氟替卡松雾化吸入,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只大鼠,收集肺组织作切片,行苏木精-伊红及Masson染色,判断肺组织肺泡炎及肺纤维化程度;行RT-PCR检测肺组织中MMP-2 mRNA及TI MP-1 mRNA的表达;行免疫组化染色,测MMP-2和TI MP-1在肺组织的表达水平;用比色法分别检测各组羟脯氨酸（HYP）含量。结果与NS组相比,BLM组第7、14、28天肺组织的肺泡炎和肺纤维化程度明显加重,HYP含量明显升高（P〈0.05）;与BLM组相比,FP组第7、14天肺组织的肺泡炎程度明显减轻（均P〈0.05）,第28天肺纤维化程度明显减轻（P〈0.05）;FP组各时间点HYP含量均较BLM组明显降低（均P〈0.05）;MMP-2 mRNA及TI MP-1 mRNA、MMP-2及TI MP-1在NS组肺脏中有微弱表达,灌注BLM后它们的表达均增强,FP组第7、14、28天MMP-2 mRNA、TI MP-1 mRNA、MMP-2及TI MP-1的表达均较BLM组降低（均P〈0.05）;BLM组MMP-2 mRNA/TI MP-1 mRNA及MMP-2/TI MP-1均较NS组减低,而第28天FP组中MMP-2 mRNA/TI MP-1 mRNA及MMP-2/TI MP-1均较BLM组升高。结论丙酸氟替卡松雾化吸入可减轻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TI MP-1的表达,并在一定程度上调整MMP-2/TI MP-1的比值。
Objective To investigate the effect of inhaled Fluticasone propionate（FP）on the expression of matrix metalloproteinases-2（MMP-2）and tissue inhibitors of metalloproteinases-1（TIMP-1）in lung tissues of rats with bleomycin（BLM）-induced pulmonary fibrosis.Methods Forty-five Wistar rats were randomly divided into 3 groups：BLM group,normal solution（NS）group and FP group.Intratracheal perfusion of BLM was done to FP group and BLM group to induce pulmonary fibrosis,while perfusion of normal solution to NS group in the same condition from 0 to 6 days after perfusion.Aerosol inhalation of FP was given to FP group but NS to other groups in the same condition.On the 7th,14th and 28th day,the rats were sacrificed,5 rats from each group each time,and the lung tissues were sectioned and dyed by HE and Masson to determine the extent of alveolitis and pulmonary fibrosis.The mRNA and protein expression of MMP-2 and TIMP-1 in rat pulmonary parenchyma was detected by using RT-PCR and immunohistochemistry respectively.The hydroxyproline（HYP）concentration was observed by colorimetry.Results On the 7th,14th and 28th day,the extent of alveolitis and pulmonary fibrosis was more severe and HYP concentration were significantly higher in BLM group than those in NS group（P0.05）.On the 7th and 14th day,the extent of alveolitis was significantly milder in FP group than in BLM group（P0.05）.On the 7th,14th and 28th day,HYP concentration was significantly reduced in FP group as compared with BLM group（P0.05）.On the 7th,14th and 28th day,the mRNA and protein expression levels of MMP-2 and TIMP-1 in BLM group were significantly higher than those in NS group（P0.05）,but those in FP group were significantly lower than those in BLM group（P0.05）.On the 28th day,the expression levels of MMP-2 mRNA/TIMP-1 mRNA and protein in FP group were significantly higher than in BLM group.Conclusion The aerosol inhalation of FP can meliorate the extent of BLM-induced alveolitis and pulmonary fibrosis in lung tissues of th
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2010年第5期667-671,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
