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六味补气方对慢性阻塞性肺疾病细胞焦亡的干预作用及机制研究OA北大核心CSTPCD

Effect and Mechanism of Liuwei Buqi Formula on Pyroptosis in Chronic Obstructive Pulmonary Disease

中文摘要英文摘要

目的 研究六味补气方对慢性阻塞性肺疾病(COPD)细胞焦亡的影响.方法 按照随机数字表法将大鼠分为正常对照组、模型组、桂龙咳喘宁组和六味补气方低、中、高剂量组,每组10只.采用烟熏加脂多糖(LPS)气管滴入的方法建立COPD大鼠模型.药物干预后,检测大鼠肺功能;支气管肺组织形态学改变;同时检测肺组织NOD样受体热蛋白结构域相关蛋白3(NLRP3)和Gasdermin D-N端(GSDMD-N)的改变;肺泡灌洗液(BALF)中炎症因子白介素18(IL-18)、白介素1 β(IL-1 β)水平;肺组织活性氧(ROS)水平;肺组织NLRP3、半胱天冬酶-1(Caspase-1)、Gasdermin D(GSDMD)、凋亡相关斑点样蛋白(ASC)蛋白表达以及mRNA水平.结果 与正常对照组比较,模型组大鼠肺功能降低(P<0.01),肺组织损伤,细胞膜破裂,IL-18、IL-1 β 和 ROS 水平升高(P<0.01),肺组织 NLRP3、Caspase-1、GSDMD、和ASC蛋白表达和mRNA水平显著升高(P<0.01,P<0.05).与模型组比较,各用药组肺功能改善,肺组织损伤和细胞焦亡减轻,IL-18、IL-1β和ROS水平下降(P<0.01),肺组织NLRP3、Caspase-1、GSDMD和ASC蛋白表达和mRNA水平降低(P<0.01),其中以六味补气方高剂量组改变最为显著.结论 六味补气方可降低COPD大鼠IL-18、IL-1β和ROS水平,减轻气道炎症和氧化应激,阻抑肺组织损伤和细胞的焦亡,增加肺功能,其机制可能是通过调控ROS/NLRP3/Caspase-1信号通路实现的.

Objective To investigate the effect of Liuwei Buqi Formula on pyroptosis in chronic obstructive pulmonary disease(COPD).Methods According to the random number table method,the rats were divided into normal control group,model group,Guilong Kechuanning group and low,medium,high dose group of Liuwei Buqi Formula,with 10 rats in each group.The experimental rats models of COPD were established by smoked and lipopolysaccharide(LPS)tracheal drip.After intervention,the pulmonary function,pathological changes in bronchopulmonary tissues and pyroptosis situation of rats were detected.Apart from that,the NOD-like receptor thermal protein domain associated protein 3(NLRP3)and GSDMD-N alterations in lung tissue,levels of inflammatory factors interleukin-18(IL-18)and interleukin-1 β(IL-1 β)in broncho alveolar lavage fluid(BALF),lung tissue reactive oxygen species(ROS)level,lung tissue protein expression and mRNA levels of NLRP3,cysteinyl aspartate specific proteinase-1(Caspase-1),GSDMD,and apoptosis-associated speck-like protein containing a CARD(ASC)were detected.Results Compared with normal control group,the model group of rats showed lung function change,lung tissue damage,cell membrane rupture,increased of IL-18,IL-1 β,ROS(P<0.01),and expression of NLRP3,Caspase-1,GSDMD,ASC protein and mRNA significantly increased in lung tissue(P<0.01,P<0.05).Compared with the model group,lung function in rats improved,lung tissue damage was alleviated,the pyroptosis was reduced,levels of IL-18,IL-1 β,ROS decreased(P<0.01),the protein and mRNA expression of NLRP3,Caspase-1,GSDMD,GSDMD-N,ASC decreased in each drug group(P<0.01).The most significant changes which in Liuwei Buqi Formula high-dose group.Conclusion Liuwei Buqi Formula could reduce IL-18,IL-1 β,ROS levels in COPD rats,decrease airway inflammation and oxidative stress,inhibit lung tissue damage and pyroptosis,and improve lung function that the mechanism may be achieved by regulating the ROS/NLRP3/Caspase-1 signaling pathway.

吴柏合;于芳春;谢桂元;赵晶燕;方远;方芳;刘向国

安徽中医药大学中西医结合学院(合肥 230012)

慢性阻塞性肺疾病;炎症反应;细胞焦亡;活性氧/NOD样受体热蛋白结构域相关蛋白3/半胱天冬酶-1信号通路;中药复方

《中国中西医结合杂志》 2024 (005)

583-591 / 9

安徽省自然科学基金资助项目(No.1708085MH222)

10.7661/j.cjim.20240413.075

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