MCC950下调NLRP3炎症小体对慢性阻塞性肺疾病模型大鼠气管重塑及嗜酸性粒细胞水平的影响

Effects of MCC950 down-regulating NLRP3 inflammatory vesicles on airway remodeling and EOS levels in rats with COPD

摘要:

目的 探究MCC950下调NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体对慢性阻塞性肺疾病（COPD）大鼠气管重塑及嗜酸性粒细胞水平的影响。方法 将60只小鼠随机分为对照组、COPD组和MCC950组。采用脂多糖联合香烟烟雾的方法复制COPD大鼠模型。HE染色分析各组大鼠肺组织病理变化；酶联免疫吸附试验（ELISA）测定各组大鼠基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶组织抑制剂-1（TIMP-1）、基质金属蛋白酶组织抑制剂-2（TIMP-2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平；Western blotting检测各组大鼠NLRP3相关蛋白表达；检测大鼠嗜酸性粒细胞及趋化因子水平。结果 与对照组比较，COPD组大鼠肺组织中NLRP3、Cleaved caspase-1和ASC蛋白相对表达量升高（P <0.05）；肺组织表现出严重病理损伤和炎症细胞大量聚集（P <0.05）；血清MMP-2、MMP-9、TNF-α和IL-6水平升高（P <0.05），TIMP-1和TIMP-2水平降低（P <0.05）；细支气管壁厚度、管壁面积和管壁面积/腔周长均增加（P <0.05）；静脉血嗜酸性粒细胞水平增加（P <0.05）。预先注射MCC950后，以上指标均得到逆转（P <0.05）。结论 MCC950下调NLRP3炎症小体后，能够影响COPD大鼠气管重塑，改善COPD大鼠的肺组织损伤，以及降低静脉血嗜酸性粒细胞的水平。

Abstract:

Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory vesicles down-regulated by MCC950 on airway remodeling and eosinophils (EOS) level in rats with chronic obstructive pulmonary disease (COPD).Methods Sixty mice were randomly divided into three groups: control group, COPD group and MCC950 treatment group. A rat model of COPD was established by lipopolysaccharide combined with smoke. HE staining, ELISA, western blot and flow cytometry were used to analyze the structural changes of lung tissue, bronchiolar wall thickness, wall area, wall area/lumen perimeter, NLRP3-related protein expression, airway remodeling-related factor levels and venous eosinophil content in each group.Results Compared with control group, the levels of NLRP3, Cleaved caspase-1 and ASC were increased in COPD group (P < 0.05). The lung tissue showed serious pathological injury and large accumulation of inflammatory cells (P < 0.05). The contents of MMP-2, MMP-9, TNF-α and IL-6 in serum were increased (P < 0.05), while the contents of TIMP-1 and TIMP-2 were decreased (P < 0.05). Bronchial wall thickness, tube wall area and tube wall area / cavity circumference were increased (P < 0.05). The content of eosinophil in venous blood was increased (P < 0.05). After pre-injection of MCC950, the above indexes were reversed (P < 0.05).Conclusion Down-regulation of NLRP3 inflammatory vesicles by MCC950 can affect airway remodeling, ameliorate lung tissue injury and decrease the content of EOS in venous blood of COPD rats.