基于IL-1β/COX-2信号通路探讨苗药吉祥草抑制COPD气道粘液高分泌的分子机制研究

Hronic obstructive pulmonary disease is a disease characterized by continuous flow limited.With the worsening of human living environment, the incidence of COPD is heighten, so it is urgent for patients and medical workers to looking for a safe and effective treatment.Studies have shown that high airway mucus secretion is one of the important pathophysiological features of COPD, which is exists in the occurrence,development stages. COPD airway mucus secretion has become a high impact condition and prognosis independent risk factor for COPD.At the present,the molecular mechanism of high COPD airway mucus secretion is not fully clear.Among them,the study based on IL - 1 beta/cox-2 signaling pathways of high airway mucus was seldom researched. At the present.Western medicine treatment of COPD airway mucus secretion is less and curative effect is poor.A large number of clinical studies have confirmed that Chinese medicine especially the folk medicine for the treatment of COPD airway mucus secretion of high effect is remarkable.In addition the miao medicine of Jixiangcao has the effect of relieving cough ,reducing sputum  and clearing away lung heat, reducing sputum, Studies have confirmed that Jixiangcao have inhibitory effect on high COPD airway mucosa secretion. This topic is based on IL - 1 beta/cox-2 signalingpathway to explore Jixiangcao molecular mechanism of high inhibition of COPD airway mucus secretion.That led to researching and developing of new drugs in the folk medicine which is treat for COPD .

COPD是一种以持续性气流受阻为特征的疾病，病情呈进行性进展，其发病率、住院率、死亡率高，给社会和经济造成沉重的负担，目前COPD的发病机制尚未完全明了，而气道粘液高分泌存在于COPD发生、发展的各个阶段，已成为影响COPD病情及预后的独立危险因素。COPD气道粘液高分泌发病机制复杂，IL-1β/COX-2信号通路是调节气道粘液高分泌的一条重要的细胞转录途径，能减少气道阻塞，改善肺功能及运动耐力，减少预后急性加重频率，目前西药抑制COPD气道粘液高分泌的药物有限而疗效不理想。苗药吉祥草具有清肺热、止咳化痰功效，大量临床证实，吉祥草能改善COPD气道粘液高分泌患者高分泌状态，减少痰液量，使痰液由稠变稀，为进一步明确其作用机制本课题拟通过基于IL-1β/COX-2信号通路探讨苗药吉祥草抑制COPD气道粘液高分泌的分子机制研究，明确其作用机制，为苗药治疗COPD以及进一步开发利用苗药打下实验基础

慢性阻塞性肺疾病（COPD）气道粘液高分泌存在于COPD发生、发展的各个阶段，已成为影响COPD病情及预后的独立危险因素，气道黏液高分泌由多种因素引起，IL-1β/COX2 信号通路是参与气道黏液高分泌的重要信号通路之一。苗药吉祥草可清肺热、止咳化痰，已广泛运用于COPD气道粘液高分泌患者，本课题基于 IL-1β/COX-2 信号通路，通过动物、细胞实验及临床研究来探讨苗药吉祥草抑制 COPD 气道黏液高分泌的分子机制。动物实验结果表明，COPD 模型组、苗药吉祥草组(低、中、高剂量组)、氨溴索组大鼠血清IL-1β、COX-2、PGE2水平及肺组织MUC5ac、TLR4蛋白及mRNA表达量均明显高于正常组，COPD模型组明显高于苗药吉祥草组、氨溴索组，氨溴索组明显高于苗药吉祥草中、高剂量组，且MUC5ac与 IL-1β、COX-2、PGE2 存在正相关的线性相关性。动物实验证实，苗药吉祥草可降低COPD大鼠血清IL-1β、COX-2、PGE2水平，下调MUC5ac表达，且一定浓度下的吉祥草作用优于氨溴索。细胞实验证实，吉祥草可抑制COPD大鼠肺泡巨噬细胞的增殖，可抑制大鼠肺泡巨噬细胞中IL-1β、PGE2和COX-2的产生。临床研究结果表明，吉祥草联合氨溴索运用于痰热郁肺型慢性阻塞性肺疾病急性加重期患者，在临床症状评分、祛痰作用疗效评价、改善肺功能以及血气分析方面均优于氨溴索组；氨溴索组及吉祥草联合氨溴索治疗组均可降低COPD患者血清IL-1β、PGE2、COX-2水平及痰、血清MUC5ac、TLR4含量，但吉祥草联合氨溴索组较氨溴索组作用明显。临床研究证实，吉祥草可降低COPD患者血清IL-1β、COX-2、PGE2水平，下调MUC5ac表达，且中西医结合治疗优于单纯西医治疗。综上，苗药吉祥草可抑制COPD气道粘液高分泌，其作用机制与其可调控IL-1β/COX2 信号通路有关。