布地奈德联合辛伐他汀对慢性阻塞性肺疾病大鼠炎症因子与肺组织病理的影响

Synergistic effect of Budesonide and Simvastatin on cytokines and lung histological injury in rat models of COPD

摘要:

目的探讨布地奈德联合辛伐他汀对慢性阻塞性肺疾病（COPD）大鼠模型炎症因子与肺组织病理的影响，为药物干预方案提供实验依据。方法根据不同的药物干预方案将COPD 大鼠分为模型组（M 组）、布地奈德组（BD 组）、辛伐他汀组（SV 组）及布地奈德联合辛伐他汀组（BD+SV 组），比较不同组别COPD 大鼠血清和支气管肺泡灌洗液（BLAF）中的白细胞介素6（IL-6）、白细胞介素8（IL-8）、白三烯B4（LTB4）、肿瘤坏死因子α（TNF-α）水平及肺组织病理的改变。结果血清炎症因子水平：BD 组IL-6、TNF-α，SV组IL-6，（BD+SV）组IL-6、IL-8 及TNF-α分别较M 组降低（均 p<0.05）；（BD+SV）组IL-8 水平较SV 组下降（p <0.05）。BALF 炎症因子水平：BD 组IL-6、IL-8，SV 组IL-6、TNF-α，（BD+SV）组IL-6、IL-8、LTB4 及TNF-α水平分别较M 组降低（均p<0.05）。（BD+SV）组BALF 中IL-8、LTB4 及TNF-α水平较BD 组降低，IL-8、LTB4水平较SV组下降（均p<0.05）。BD组、SV组、（BD+SV）组肺组织病理半定量评分较M组降低（均p<0.05），病理均显示肺气肿囊腔变小、支气管炎症减轻。结论使用布地奈德联合辛伐他汀可以有效降低COPD 大鼠全身和气道炎症反应，改善肺组织病理。

Abstract:

Objective To investigate synergistic effect of Budesonide and Simvastatin on cytokines and pulmonary histological injury in rat models of chronic obstructive pulmonary disease (COPD) so as to provide indications for novel pharmacological intervention. Methods Rats were randomly divided into model (M) group,Budesonide (BD) group, Simvastatin (SV) group and Budesonide combined with Simvastatin (BD+SV) group.Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), leukotriene B4 (LTB4) and tumor necrosis factor alpha(TNF-α) in serum and bronchoalveolar lavage fluid (BALF) were measured. Histological injury was graded in rat lung slices. Results Inflammatory cytokines in serum: compared with the M group, levels of IL-6 and TNF-α in the BD group, IL-6 in the SV group, and IL-6, IL-8 and TNF-α in the BD+SV group were decreased (p < 0.05). The level of IL-8 was attenuated in the BD+SV group compared with those in the SV group (p < 0.05). Inflammatory cytokines in BALF: the levels of IL-6 and IL-8 in the BD group, IL-6 and TNF-αin the SV group, and IL-6, IL-8, LTB4 and TNF-α in the BD+SV group were reduced compared with those in the M group (p < 0.05). Levels of IL-8, LTB4 and TNF-α in the BD+SV group were decreased in comparison with those in the BD group. Levels of IL-8 and LTB4 could be diminished by BD+SV treatment when compared with the SV group (p < 0.05). Semi-quantitative scores of pathological changes of lung tissues in the BD group, the SV group and the BD+SV group were lower than those in the M group (p <0.05), the lung tissues showed reduced cyst cavities and alleviated bronchitis. Conclusions Budesonide combined with Simvastatin could synergistically relieve systematic and airway inflammation, and attenuate histological injury in the lungs of COPD rat models.