摘要
目的研究阿托伐他汀对博莱霉素诱导的大鼠肺纤维化的调节作用及其机制。方法雄性Wistar大鼠32只随机分为阿托伐他汀干预组(A组)、博来霉素组(B组)及正常对照组(C组)大鼠气管内灌注博来霉素5 mg/kg建立肺纤维化模型,A组在博莱霉素后给予阿托伐他汀灌胃10 mg/(kg.d),分别于第7、28天处死一半,病理学观察肺泡炎及肺纤维化程度,生化法测定肺组织羟脯氨酸含量,ELISA法检测肺泡灌洗中IFN-γ、IL-4的浓度,比较组间变化。结果与C组相比,B组大鼠出现明显的肺泡炎及纤维化,而阿托伐他汀可显著减轻肺纤维化程度。BALF中,B组IL-4升高而IFN-γ降低,阿托伐他汀干预可部分逆转这种变化。结论阿托伐他汀可能通过调节Th1/Th2平衡而减轻博莱霉素诱导的大鼠肺纤维化。
【Objective】 To study the immunoregulatory effect of Atorvastatin,a 3-hydroxy-3-methyl-glutaryl coenzyme A（HMG-CoA） reductase inhibitor,on Bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.【Methods】 Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of Bleomycin（5 mg/kg）.Subsequently,the rats received daily Atorvastatin（10 mg/kg） orally.Four to six rats in each group were sacrificed 7 and 28 days after intratracheal instillation.Histological changes in the lungs were evaluated by hematoxylin-eosin and masson stain and scored.Hydroxyproline contents in lung tissues were detected.The levels of IFN-γ and IL-4 in bronchoalveolar lavage fluid（BALF） were measured by ELISA.【Results】 Inflammatory cell infiltration and fibrotic scores were more prominent in the model group compared to the control group.Hydroxyproline contents in lung tissue were significantly increased 28 days after intratracheal Bleomycin instillation.Atorvastatin apparently attenuated the degree of pulmonary fibrosis.Further study showed that Atorvastatin significantly increased IFN-γ levels while decreasing IL-4 levels in lung BALF.【Conclusions】 Atorvastatin had an inhibitory effect on Bleomycin-induced pulmonary fibrosis.This effect may be associated with its regulation on Th1/Th2 balance in the lung.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2011年第8期919-923,共5页
China Journal of Modern Medicine
