肺康颗粒对COPD大鼠miRNA-21、TGF-β/Wnt-5a信号通路的影响及机制  

Study on the effect of Feikang Granules on COPD rats and its mechanism based on miRNA-21 regulation of TGF-β/Wnt-5a signaling pathway.

作　　者：张高[1] 黄楚栓 褚庆民[1] 杨柳柳[1] ZHANG Gao;HUANG Chu-shuan;CHU Qing-min;YANG Liu-liu(Department of Respiratory,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510145,Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院呼吸科,广东广州510145

出　　处：《广东医学》2022年第5期529-533,共5页Guangdong Medical Journal

基　　金：国家自然科学基金青年项目(81904132);广东省中医药局中医药科研立项项目(20212056);广东省自然科学基金项目(2017A030313745)。

摘　　要：目的基于微小核糖核酸(miR)-21调控转录生长因子-β(TGF-β)/无翅和整合位点生长因子5a(Wnt-5a)信号通路,探讨肺康颗粒干预慢性阻塞性肺疾病(COPD)大鼠炎症的机制。方法将90只SD大鼠随机分成6组:空白对照组、模型组、地塞米松组及肺康颗粒低、中、高剂量组。采用烟熏加气管内注入内毒素法建立大鼠COPD模型。第5周开始给予肺康颗粒灌胃干预,连续给药16周。肺功能检测仪检测大鼠用力肺活量(FVC)、第0.3秒用力呼气容积(FEV0.3)、第0.3秒用力呼气容积与用力肺活量的比(FEV0.3/FVC%)。酶联免疫吸附法(ELISA)测定大鼠血浆、支气管肺泡灌洗液(BALF)炎症细胞因子转录生长因子-β、白细胞介素(IL)-8、IL-17A含量;qRT-PCR法检测肺组织中miRNA-21、Wnt-5a、TGF-βmRNA表达。结果与空白对照组比较,模型组、地塞米松组及肺康颗粒各剂量组大鼠FEV0.3、FVC以及FEV0.3/FVC均显著下降(P<0.05);与模型组比较,肺康颗粒各剂量组的TGF-β、IL-8、IL-17A含量明显降低(P<0.01);肺康颗粒各剂量组的miR-21、Wnt-5a mRNA、TGF-β表达明显下调(P<0.01)。结论肺康颗粒可能通过TGF-β/Wnt-5a信号转导通路干预miR-21炎症基因的表达,减轻COPD大鼠的炎症反应。Objective Based on miRNA-21 regulation of TGF-β/Wnt-5a signaling pathway,to investigate the mechanism of Feikang Granules interfering with chronic obstructive pulmonary disease(COPD)inflammation in rats.Methods Eighty SD rats were randomly divided into 4 groups,blank control group,model group,Feikang granule group and budesonide group.The rat model of COPD was established by the method of injecting endotoxin into the airway by smoking.From the 5th week,Feikang granules were given intragastric intervention for 2 weeks.The lung function,inclu-ding forced vital capacity(FVC),the forced expiratory volume in the first 0.3 second(FEV0.3),and the ratio of the forced expiratory volume in the first second to the forced vital capacity(FEV0.3/FVC%),were tested.Enzyme-linked immunosorbent assay(ELISA)was used to determine the contents of inflammatory cytokines,TGF-β,IL-8,and IL-17A,in rat BALF and serum;and qRT-PCR method was used to detect the expression of miRNA-21,Wnt-5 and TGF-βmRNA,in lung tissue.Results Pulmonary function showed that the FEV0.3,FVC and FEV0.3/FVC were significantly reduced(P<0.05).Compared with the model group,the contents of TGF-β,IL-8 and IL-17A in the Feikang granule group were significantly reduced(P<0.01).The expression of miRNA-21,Wnt-5 and TGF-βmR-NA in the Feikang granule group was significantly down-regulated(P<0.01).Conclusion Feikang granules may in-terfere with the expression of miR-21 inflammatory genes through the TGF-β/Wnt-5a signal transduction pathway,and reduce the inflammatory response in COPD rats.

关 键 词：肺康颗粒 慢性阻塞性肺疾病 TGF-β/Wnt-5a信号通路 miR-21基因 炎症 

分 类 号：R563.3[医药卫生—呼吸系统] R714.253[医药卫生—内科学]