辛伐他汀对慢性阻塞性肺疾病模型大鼠气道炎症和气道黏液高分泌的防治作用及其机制  

Effects of simvastatin on airway inflammation and airway mucus hypersecretion in rats with chronic obstructive pulmonary disease

作　　者：王胜[1] 熊玲玲[1] 邓雪[1] 任薇[1] 朱春冬[1] 李春颖[1] 周群[1] 

机构地区：[1]安徽中医药大学第一附属医院干部呼吸内科,合肥230031

出　　处：《中华医学杂志》2015年第22期1726-1730,共5页National Medical Journal of China

基　　金：安徽高校省级自然科学研究项目（KJ20132182）

摘　　要：目的 探讨辛伐他汀对慢性阻塞性肺疾病（慢阻肺）模型大鼠气道炎症和气道黏液高分泌的防治作用及其机制.方法 采用烟熏和大鼠气管内注入脂多糖的方法建立慢阻肺模型.将18只雄性SD大鼠按随机数字表法随机均分为对照组、慢阻肺组、辛伐他汀组各6只.对照组和慢阻肺组用生理盐水1 ml/100 g灌胃,1次/d;辛伐他汀组用辛伐他汀溶液（0.5 g/L）1 ml/100 g灌胃,1次/d.肺功能仪检测大鼠肺功能,HE染色观察大鼠支气管、肺组织病理变化.酶联免疫吸附（ELISA）法检测各组大鼠支气管肺泡灌洗液（BALF）中白细胞介素（IL）-8、IL-17及肿瘤坏死因子（TNF）-α含量.免疫组织化学法检测大鼠气道中黏附分子1、核因子（NF）-κB、黏蛋白5AC和Toll样受体4（TLR4）蛋白的表达.Western印迹法检测大鼠支气管肺组织中黏蛋白5AC和TLR4蛋白的表达.荧光实时定量（RT）-PCR检测大鼠支气管肺组织中黏蛋白5AC mRNA和TLR4 mRNA的表达.结果 慢阻肺组支气管、肺组织改变符合慢阻肺的病理表现.与对照组相比,辛伐他汀组支气管肺组织均出现不同程度损伤,但损伤程度轻于慢阻肺组.辛伐他汀组肺功能显著低于对照组,但优于慢阻肺组.辛伐他汀组BALF中IL-8、IL-17、TNF-α含量分别为（484.4±11.1）、（78.9±2.0）、（192.7±2.0）ng/L,均显著低于慢阻肺组的（605.0 ±48.7）、（89.9±6.9）、（212.6±10.7）ng/L,但均显著高于对照组的（341.2±21.4）、（56.0±2.9）、（127.5±9.0）ng/L（均P＜0.01）.辛伐他汀组支气管肺组织中黏附分子1、NF-κB、黏蛋白5AC和TLR4蛋白的表达均显著低于慢阻肺组,但均显著高于对照组（均P＜0.01）.辛伐他汀组支气管肺组织中黏蛋白5AC mRNA和TLR4 mRNA及其蛋白的表达均显著低于慢阻肺组（均P＜0.05）.结论 辛伐他汀可降低慢阻肺模型大鼠BALF中IL-8、IL-17、TNF-α水平,抑制气道和肺组织内黏附分子1、NF-κB�Objective To explore the preventive and therapeutic effects of simvastatin on rats with chronic obstructive pulmonary disease （COPD） and examine the mechanism of airway inflammation and airway mucus hypersecretion.Methods The rat model of COPD was established by cigarette smoking and an intratracheal injection of lipopolysaccharide （LPS）.A total of 18 male Sprague-Dawley rats were randomly divided into control,COPD and simvastatin groups （n =6 each）.The control and COPD groups received normal saline once daily via intragastric administration （i.g.） while the simvastatin group had simvastatin （0.5 g/L） 1 ml/100 g once daily via i.g.Pulmonary function was tested and pathological changes in bronchus and lung were observed.The bronchoalveolar lavage fluid （BALF） levels of interleukin-8 （IL-8）,interleukin-17 （IL-17） and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）.The protein expressions of intercellular adhesion molecule 1 （ICAM-1）,nuclear factor κB （NF-κB）,mucin 5AC （MUC5AC） and Toll-like receptor 4 （TLR4） in rat airway were detected by immunohistochemical staining.The mRNA and protein expressions of TLR4 and MUC5AC in bronchi and lung tissue were detected by fluorescent real time quantitative polymerase chain reaction （RT-PCR） and Western blot.Results The changes of bronchi and lung tissues in COPD group were consistent with typical pathological manifestations of COPD.As compared with the COPD group,the degree of pulmonary pathological damage and the decline of pulmonary function in the simvastatin group were significantly lessened,but still remarkable as compared with the control group.The BALF levels of IL-8,IL-17 and TNF-α in the smvastatin group [（484.4 ± 11.1）,（78.9 ± 2.0）,（192.7 ± 2.0） ng/L] were significantly lower than those in the COPD group [（605 ±48.7）,（89.9 ±6.9）,（212.6 ± 10.7） ng/L],but still higher than those in the control group [（341.2 ± 21.4）,（56.0 ± 2.9�

关 键 词：肺疾病 慢性阻塞性 辛伐他汀 气道炎症 气道黏液高分泌 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统] R-332[医药卫生—内科学]