阿托伐他汀缓解百草枯中毒大鼠肺纤维化机制的研究  

A Mechanisms Study on Atorvastatin in Alleviation of Pulmonary Fibrosis Rats with Paraquat Poisoning

作　　者：龚晓亮[1] 樊菲菲[1] 王彦军[1] 黄杨[1] 尹文[1] 

机构地区：[1]第四军医大学西京医院急诊科,西安710032

出　　处：《解放军医药杂志》2015年第5期23-25,32,共4页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金(8110413)

摘　　要：目的观察阿托伐他汀对百草枯中毒所致肺纤维化疗效,并探讨其可能的作用机制。方法取健康成年SD大鼠120只,随机分为生理盐水组和百草枯组,每组10只,百草枯+阿托伐他汀10、20、40 mg组(实验1、2、3组),百草枯+阿托伐他汀40 mg+吡格列酮组(PLZ组)和百枯草+阿托伐他汀40 mg+GW9662组(GW9662组),每组20只。百草枯肺间质纤维化模型以百草枯溶液3.5 mg/kg的剂量腹腔注射制备,生理盐水组则以等体积的生理盐水腹腔注射,其余各药物干预组均在建立百草枯模型的基础上给予相应的药物,连续给药14 d后处死大鼠,比较各组大鼠肺泡灌洗液中炎性细胞数目、肺组织中羟脯氨酸、血清中转化生长因子(TGF)-β1的含量。结果肺泡灌洗液中炎性细胞数目、肺组织中羟脯氨酸、血清中TGF-β1的含量百草枯组均高于生理盐水组,实验2、3组均低于百草枯组(P<0.05,P<0.01)。GW9662组肺泡灌洗液中炎性细胞数目和肺组织中羟脯氨酸低于实验3组,PLZ组高于实验3组(P<0.05,P<0.01)。GW9662组和PLZ组血清中TGF-β1的含量均高于实验3组,但PLZ组升高更明显(P<0.05,P<0.01)。结论阿托伐他汀可缓解百草枯中毒所致的肺纤维化,且呈剂量依赖的方式,其作用机制可能是通过PPARγ途径而实现。Objective To observe the curative effects of Atorvastatin on Paraquat（PQ）-induced pulmonary fibrosis and to explore the possible mechanisms. Methods A total of 120 healthy adult SD rats were randomly divided into normal saline group（ n = 10）,PQ poisoned group（ n = 10）,PQ and Atorvastatin at the dose of 10,20 or 40 mg groups（experiment group 1,2 and 3,n = 20 for each group）,PQ,Atorvastatin at the dose of 40 mg and Pioglitazone group（PLZ group,n = 20） and PQ,Atorvastatin at the dose of 40 mg and GW9662 group（GW9662 group,n = 20）. The PQinduced pulmonary fibrosis models were established with 3. 5 mg / kg PQ solutions by intraperitoneal injection,and the models of normal saline group were established with the same volume of normal saline by intraperitoneal injection. All the drug intervention groups were given corresponding drugs after the establishment of PQ models,and all the SD rats were sacrificed at the 14 thd of continous administration,and then the amount of inflammatory cells in alveolar lavage fluid,the content of hydroxyproline in lung tissues and the content of serum TGF-β1（ transforming growth factor-β1） among all groups were compared. Results The values of amount of inflammatory cells in alveolar lavage fluid,the content of hydroxyproline in lung tissues and the content of serum TGF-β1in PQ poisoned group were significantly higher than those in normal saline group,and the values in experiment group 2 and 3 were less significant than those in PQ group（ P〈0. 05,P〈0. 01）. The values of amount of inflammatory cells in alveolar lavage fluid and the content of hydroxyproline in lung tissues in GW9662 group were less significant than those in experiment group 3,while the values in PLZ group were significantly higher than those in experiment group 3（ P〈0. 05,P〈0. 01）. The values of serum TGF-β1content in PLZ group and GW9662 were significantly higher than that in experiment group 3,but the increased value was more obvious in PLZ group（ P〈0. 05,P〈0. 01）. Con

关 键 词：百草枯 中毒 肺纤维化 阿托伐他汀 吡格列酮 GW9662 PPARγ 大鼠 Sprague-Dawley 

分 类 号：R595.5[医药卫生—内科学]