信号通路探讨止咳定喘汤治疗慢性阻塞性肺疾病作用机制的实验研究  

An experimental study on the mechanism of the Zhike Dingchuan decoctionon treating chronic obstructive pulmonary disease by TLR4/NF-κB signalingpathway intervention

作　　者：陈旭[1] 薛晓明[1] 王洋[1] 关炜[1] 张莉[1] 周波波[1] 张罗丹 尚芳[1] Chen Xu

机构地区：[1]山西省中医院,山西太原030000

出　　处：《中医临床研究》2019年第34期7-10,共4页Clinical Journal Of Chinese Medicine

基　　金：山西省科技厅项目,项目编号:201703D321021。

摘　　要：目的:观察止咳平喘汤对慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease,COPD)大鼠肿瘤坏死因子-α(Tumor Necrosis Factor,TNF-α)、白介素-8(Interleukin-8,IL-8)、血管内皮细胞生长因子(Vascular Endothelial Growth Factorr,VEGF)、肺组织的影响,探讨止咳定喘汤可能通过干预TLR4/NF-κB信号通路抑制炎症表达的作用机制。方法:将60只SD大鼠随机分为6组,分别为正常组、模型组、止咳定喘汤低剂量、止咳定喘汤中剂量、止咳定喘汤高剂量组、地塞米松组,每组10只,采用经典慢性阻塞性肺疾病大鼠模型(烟熏联合气道内注射脂多糖法)。空白组和模型组以蒸馏水灌胃,对照组以地塞米松混悬液灌胃;其余治疗组以止咳定喘汤灌胃,干预30天后,采用酶联免疫吸附试验(ELISA)法测定大鼠支气管肺泡灌洗液中的炎性指标:IL-8、VEGF、TNF-α;采用苏木素-伊红染色观察大鼠肺组织病理形态学的改变,采用Western Blot法检测肺组织细胞胞浆蛋白TLR4、p-IκB、IκB及胞核蛋白NF-κBp65的蛋白表达。结果:与模型组比较,止咳定喘汤各剂量组治疗后肺组织均有所改善;止咳定喘汤各组的大鼠血清TNF-α、IL-8表达水平明显均有下降趋势、VEGF表达水平明显有上升趋势,差异有统计学意义(P<0.05);止咳定喘汤各剂量组的TLR4、IκB蛋白表达明显上调(P<0.05),胞核蛋白NF-κBp65的表达明显下调(P<0.05)。结论:止咳定喘汤可能通过TLR4/NF-κB信号转导通路干预炎症因子的表达,减轻慢性阻塞性肺病大鼠的炎症反应。Objective:To investigate efficacy of the Zhike Dingchuan decoction(止咳定喘汤)on inflammatory reaction of chronic obstructive pulmonary disease by TLR4/NF-κB signaling pathway intervention.Methods:Sixty SD rats were randomly divided into the normal group,the model group,the Zhike Dingchuan decoction low dose,medium dose and high dose group and the dexamethasone group,10 rats in each group.After 30 days of intervention with the Xuanfei Pingchuan capsule(宣肺平喘胶囊),the inflammatory markers in the bronchoalveolar lavage fluid of rats,IL-8,VEGF and TNF-κwere determined by enzyme-linked immunosorbent assay.Protein expression of TLR4,p-IκB,IκB and nuclear protein NF-κB p65 in lung tissue cell cytoplasm were tested by Western Blot;pathological changes in rat lung tissue were observed by hematoxylin-eosin staining.Results:After treatment,compared with the model group,the lung tissue of the Zhike Dingchuan decoction high middle and low dose groups were improved.The levels of TNF-αand IL-8 in the Zhike Dingchuan decoction middle and high dose groups were significantly decreased(P<0.05).The expressions of TLR4 and IκB in the Zhike Dingchuan decoction high,middle and low dose groups were significantly up-regulated(P<0.05),and the expression of p65 was down-regulated(P<0.05).Conclusion:The Zhike Dingchuan decoction can interfere with the expression of in flammatory factors through TLR4/NF-κB signal transduction pathway and reduce the inflammatory response in rats with chronic obstructive pulmonary disease.

关 键 词：Toll样受体/核因子-κB 止咳定喘汤 慢性阻塞性肺炎 

分 类 号：R541.6[医药卫生—心血管疾病]