Expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease with a cold-dryness symptom pattern

OBJECTIVE: To reveal the effects on expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease(COPD) and a cold-dryness symptom pattern induced by elastase and smoking.METHODS: The COPD model was established with an elastase dose into the trachea combined with exposure to smoking; the COPD model cold-dryness symptom pattern was further developed by exposure to a cold, dry environment. After 90 days,pathologic lung sections, inflammatory cytokine levels(measured by enzyme linked immunosorbent assay), m RNA and protein expression of mucus-associated proteins and aquaporins(measured by real-time polymerase chain reaction and western blots) were examined.RESULTS: Cytokines interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α) in the COPD and the cold-dryness symptom pattern COPD groups were all significantly higher than in controls(each P < 0.01). IL-6 and IL-8 levels were higher in the cold-dryness symptom pattern COPD group than in the COPD group(each P < 0.05). The AQP5 m RNA expression in the cold-dryness symptom pattern COPD and COPD groups was lower than in the control group(P < 0.01), and that in the cold-dryness symptom pattern COPD group was lower than the COPD group(P < 0.05). The expression of MUC5 AC and MUC5 B m RNAs in the cold-dryness symptom pattern COPD group and COPD group was higher than in the control group(each P < 0.01), and that in the cold-dryness symptom pattern COPD group was higher than the COPD group(P < 0.01, and P < 0.05, respectively).The ratio of MUC5 AC m RNA/MUC5 B m RNA was COPD group < the cold-dryness symptom pattern COPD group < the control group. AQP4 and AQP5 protein expression in the cold-dryness symptom pattern COPD group was lower than that in the COPD group which was lower again than in the control group. MUC5 AC and MUC5 B expression in the cold-dryness symptom pattern COPD group was higher than in the COPD group and higher again than in the control group.CONCLUSION: Cold-dryness affects the expression of mucus-associated protein m RNA and its corresponding proteins, reducing the secretion of aquaporins and increasing the secretion of mucins. Imbalance in aquaporins and mucins can affect the function of mucus, increasing airway obstruction.

黏蛋白1与呼吸系统疾病关系的研究进展

慢性黏液高分泌导致的气道炎症可能会逐渐进展并影响患者的肺功能。黏液蛋白是黏液层的关键成分,其中黏蛋白1是一种重要的膜结合型黏蛋白,目前的研究聚焦于评估黏蛋白1在肺纤维化、肺癌和间质性肺疾病等肺部疾病中的临床应用,尤其是作为诊断、预测进展和评估治疗效果的生物标志物。因此,深入了解黏蛋白1在肺部疾病中的生物学机制和作用方式,特别是与疾病发展和进展的关联,探索黏蛋白1在肺部疾病早期诊断和预后评估中的预测价值,将为肺部疾病的诊断和治疗提供新的理论依据。

参七化痰方对慢性阻塞性肺疾病模型大鼠气道水通道蛋白2、5、6和黏蛋白5AC表达影响

目的：通过观察参七化痰方对慢性阻塞性肺疾病模型大鼠气道水通道蛋白2、5、6和黏蛋白5AC表达的影响,探讨其治疗慢性阻塞性肺疾病的可能作用机理。方法：200只清洁级健康雄性Wistar大鼠随机分为正常组、COPD模型组、参七化痰方治疗组（治疗组）、羧甲司坦治疗组（对照组）,采用烟熏结合气管注射脂多糖方法复制COPD模型,模型组和治疗组、对照组随机选取模型复制成功的大鼠20只进行实验,观察各组大鼠气道AQP2、AQP5、AQP6和MUC5AC表达变化情况。结果：COPD模型复制成功以后,AQP2、AQP5和AQP6在气道中的表达显著减少（P〈0.01）,气道MUC5AC的含量显著增多（P〈0.01）;在用参七化痰方和羧甲司坦治疗后,AQP2、AQP5和AQP6含量均显著增多（P〈0.05或P〈0.01）,气道MUC5AC的含量均显著降低（P〈0.01）;与羧甲司坦治疗比较,参七化痰方治疗组的AQP2、AQP5、AQP6和MUC5AC含量差异不显著（P〉0.05）。结论：参七化痰方可以有效地改善COPD状态下模型大鼠气道AQP2、AQP5、AQP6和黏蛋白MUC5AC的表达,改善黏液高分泌状态。

爱罗咳喘宁对COPD大鼠气道水通道蛋白5和黏蛋白5AC基因表达的影响

目的:观察爱罗咳喘宁对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠模型气管、支气管组织中水通道蛋白5(aquaporin5,AQP5)与黏蛋白5AC(mucin 5AC,MUC5AC)表达的影响。方法:采用脂多糖(lipopolysaccharide,LPS)加烟雾诱导COPD大鼠模型,大鼠随机分为正常组、模型组、急支糖浆组、爱罗咳喘宁低、中、高剂量组。正常组、模型组ig生理盐水(15.52 m L·kg-1·d-1),急支糖浆组给予太极急支糖浆(10 m L·kg-1·d-1)灌胃,爱罗咳喘宁低、中、高剂量组分别ig(7.75,15.52,31.04 g·kg-1·d-1),连续14 d。原位杂交和免疫组化检测AQP5与MUC5AC在气管、支气管组织中的原位表达。结果:与正常组相比,模型组大鼠AQP5 mRNA和蛋白表达均减弱,MUC5AC mRNA和蛋白表达均增强,AQP5蛋白与MUC5AC蛋白表达呈负相关(r=-0.50,P<0.01);与模型组相比,爱罗咳喘宁中剂量组AQP5基因表达增强,MUC5AC基因表达减弱,AQP5蛋白与MUC5AC蛋白表达呈负相关(r=-0.45,P<0.01)。结论:爱罗咳喘宁调节COPD气道黏液高分泌的作用机制可能与上调AQP5、抑制MUC5AC基因表达有关。