摘要
目的:分析瑞舒伐他汀对慢性阻塞性肺疾病(COPD)大鼠气道炎症的抑制作用及对TLR4/NF-κB信号通路的影响。方法:利用烟熏及气道灌入脂多糖的方法建立大鼠COPD模型。60只SD大鼠随机分为对照组(n=20)、COPD组(n=20)、瑞舒伐他汀组(n=20)。瑞舒伐他汀组大鼠5.0 mg·kg^(-1)的瑞舒伐他汀,每日灌胃1次。检测各组大鼠的肺功能指标如肺活量(FVC)、呼气峰值流速(PEF)以及0.1 s呼气量(FEV0.1)及肺组织病理变化。酶联免疫吸附法检测血清白细胞介素(IL)-6、IL-8与肿瘤坏死因子(TNF)-α含量。Western印迹法检测肺组织NF-κB、黏附分子1、黏蛋白5AC、TLR4蛋白表达。荧光定量PCR法检测肺组织NF-κB、黏附分子1、黏蛋白5AC、TLR4 mRNA表达。结果:COPD组各项肺功能指标显著低于对照组(P<0.05),瑞舒伐他汀组显著高于COPD组(P<0.05)。显微镜下观察,对照组肺泡组织结构正常。COPD组肺泡壁显著变薄,且肺泡出现破裂、融合,肺大疱形成,周围可见炎细胞浸润。瑞舒伐他汀组肺损伤明显轻于COPD组。COPD组IL-6、IL-8与TNF-α的含量显著高于对照组(P<0.05),而瑞舒伐他汀组显著低于COPD组(P<0.05)。COPD组大鼠肺组织中黏附分子1、黏蛋白5AC、NF-κB及TLR4蛋白及mRNA水平均显著高于对照组(P<0.05),而瑞舒伐他汀组显著低于对照组(P<0.05)。结论:瑞舒伐他汀可有效降低COPD大鼠气道炎性反应,其机制可能与降低NF-κB及TLR4表达,抑制TLR4/NF-κB信号通路活性,并降低黏液蛋白的高分泌状态,减轻气道炎性介质的释放有关。
OBJECTIVE To analyze the inhibitory effect of rosuvastatin on airway inflammation in rats with chronic obstructive pulmonary disease(COPD)and its effect on TLR4/NF-κB signaling pathway.METHODS Rat model of COPD was established by smoking and airway instillation of lipopolysaccharide.60 SD rats were randomly divided into normal group(n=20),COPD group(n=20)and rosuvastatin group(n=20).Rosuvastatin rats were treated with 5.0 mg·kg-1rosuvastatin once daily.The lung function indices(such as vital capacity(FVC),peak expiratory flow(PEF)and 0.1 s expiratory volume(FEV0.1)and lung pathological changes were measured in each group.The levels of serum interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor(TNF)-αwere determined by enzyme-linked immunosorbent assay.Western blotting was used to detect the expression of NF-κB,adhesion molecule 1,mucin 5 AC and TLR4 in lung tissue.The expression of NF-κB,adhesion molecule 1,mucin 5 AC,and TLR4 mRNA in lung tissue was detected by fluorescent quantitative PCR.RESULTS The lung function indexes in the COPD group were significantly lower than those in the control group(P<0.05).The rosuvastatin group was significantly higher than the COPD group(P<0.05).Under the microscope,it was observed that the control group alveolar tissue structure is normal.In the COPD group,the alveolar wall was significantly thinner,and the alveolar bursts and fusion occurred.The lung bullae formed and peripheral inflammatory cells infiltrated.Lung injury in rosuvastatin group was significantly less severe than COPD group.The levels of IL-6,IL-8 and TNF-αin the COPD group were significantly higher than those in the control group(P<0.05),while those in the rosuvastatin group were significantly lower than those in the COPD group(P<0.05).The protein and mRNA levels of adhesion molecule 1,mucin 5 AC,NF-κB and TLR4 in lung tissue of COPD group were significantly higher than those in control group(P<0.05),while those in rosuvastatin group were significantly lower than those in control group(P<0.05).
作者
石雅娴
隗世波
刘俊
钟群琼
陈勇
刘青云
王军梅
SHI Ya-xian;HUAI Shi-bo;LIU Jun;ZHONG Qun-qiong;CHEN Yong;LIU Qing-yun;WANG Jun-mei
出处
《中国医院药学杂志》
CAS
北大核心
2019年第7期666-669,共4页
Chinese Journal of Hospital Pharmacy
基金
湖北省教育厅科研项目计划(编号:B20148395)