他汀类药物对慢性阻塞性肺疾病大鼠气道炎症及黏液高分泌的作用及机制

发布时间：2019-01-15 23:04

【摘要】：目的探讨他汀类药物对慢性阻塞性肺疾病(COPD)模型大鼠气道炎症及黏液高分泌的作用及机制。方法通过烟熏和气管注入脂多糖建立大鼠COPD模型。将21只SD大鼠随机分为对照组、COPD组、辛伐他汀组,每组7只。对照组、COPD组每日用生理盐水灌胃1次,剂量为1 ml/100 g;辛伐他汀组每日用0.5 g/L的辛伐他汀溶液按1 ml/100 g剂量灌胃1次。检测大鼠肺功能指标,苏木素-伊红(HE)染色观察支气管和肺组织的病理变化;酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)上清液中细胞因子白细胞介素(IL)-8、IL-17、肿瘤坏死因子(TNF)-α含量;免疫组化法检测肺组织中核转录因子(NF)-κB、黏附分子1、黏蛋白5AC、Toll样受体(TLR)4的表达;Western印迹和RT-PCR检测肺组织黏蛋白5AC、TLR4蛋白和mRNA的表达。结果辛伐他汀组大鼠肺功能指标明显高于COPD组,低于对照组(P0.01);辛伐他汀组大鼠病理学改变较COPD组明显减轻。COPD组大鼠BALF中IL-8、IL-17、TNF-α含量明显高于辛伐他汀组和对照组,辛伐他汀组明显高于对照组(P0.01)。COPD组、辛伐他汀组大鼠肺组织中NF-κB、黏附分子1、黏蛋白5AC、TLR4水平均明显高于对照组而低于COPD组(P0.01)。COPD组大鼠组织黏蛋白5AC、TLR4蛋白和mRNA表达量均明显高于对照组,辛伐他汀组明显低于COPD组(P0.01);辛伐他汀组与对照组之间差异无统计学意义(P0.05)。结论辛伐他汀可有效降低COPD大鼠的气道炎性反应,抑制气道黏液高分泌,主要通过抑制NF-κB下游信号通路和TLR4/NF-κB信号通路来实现。
[Abstract]:Objective to investigate the effect and mechanism of statins on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease (COPD). Methods the rat COPD model was established by fumigation and endotracheal injection of lipopolysaccharide. Twenty-one SD rats were randomly divided into control group, COPD group and simvastatin group with 7 rats in each group. In control group, COPD group was given normal saline once a day, and simvastatin group was given 1 ml/100 / g simvastatin solution once a day. Lung function and hematoxylin-eosin (HE) staining were used to detect the pathological changes of bronchi and lung tissues in rats. The levels of cytokine (IL)-8 and tumor necrosis factor (TNF)-伪 in (BALF) supernatant of bronchoalveolar lavage fluid were detected by enzyme linked immunosorbent assay (ELISA). The expression of nuclear transcription factor (NF)-魏 B, adhesion molecule 1 and mucin 5 ACU Toll-like receptor (TLR) 4 in lung tissue was detected by immunohistochemistry, and the expression of TLR4 protein and mRNA in lung tissue was detected by Western blot and RT-PCR. Results the pulmonary function index of simvastatin group was significantly higher than that of COPD group and lower than that of control group (P0.01). The content of IL-8,IL-17,TNF- 伪 in BALF in COPD group was significantly higher than that in simvastatin group and control group, and the level of IL-8,IL-17,TNF- 伪 in simvastatin group was significantly higher than that in control group (P0.01). COPD group). The levels of NF- 魏 B, adhesion molecule 1 and mucin 5ACTLR4 in simvastatin group were significantly higher than those in control group and lower than those in COPD group (P0.01). COPD group, rat tissue mucin 5ACTLR4 protein and mRNA expression were significantly higher than those in control group. Simvastatin group was significantly lower than COPD group (P0.01). There was no significant difference between simvastatin group and control group (P0.05). Conclusion Simvastatin can effectively reduce airway inflammatory response and inhibit airway mucus hypersecretion in COPD rats, mainly by inhibiting downstream NF- 魏 B signaling pathway and TLR4/NF- 魏 B signaling pathway.
【作者单位】：白城医学高等专科学校;
【基金】：吉林省教育厅“十二五”规划项目(No.20140126)
【分类号】：R563.9

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