清金化痰汤对慢阻肺模型大鼠气道炎症及气道粘液高分泌影响
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摘要
目的:分析清金化痰汤对慢性阻塞性肺疾病(COPD)模型大鼠气道炎症及气道粘液高分泌影响。方法:选取SPF级Wistar雄性大鼠45只,随机数字表法将分成三组,正常组、模型组和观察组,每组各15只,观察组和模型组大鼠制备COPD模型,从开始实验至成功造模后四周,观察组大鼠采用剂量为2. 16g/kg清金化痰汤灌胃,正常组和模型组大鼠使用同剂量生理盐水灌胃,每天一次。采用动物呼吸机检测大鼠用力肺活量(FVC)、呼气峰值流速(PEF)及0. 1秒用力呼气容积(FEV0. 1),ELISA法检测支气管肺泡灌洗液(BALF)内肿瘤坏死因子-α(TNF-α)、白细胞介素-17 (IL-17)及白细胞介素-8 (IL-8)含量,Western blot检测肺组织内Toll样受体4 (TLR4)、MUC5ac表达状况。结果:模型组和观察组大鼠PFE、FEV0. 1及FVC比正常组下降,观察组下降幅度低于模型组,差异均有统计学意义(P<0. 05);模型组和观察组大鼠TNF-α、IL-17及IL-8含量均比正常组上升,观察组上升幅度低于模型组,差异均有统计学意义(P<0. 05);模型组大鼠肺组织内TLR4、MUC5ac蛋白表达比正常组上升,观察组比模型组下降,差异均有统计学意义(P<0. 05);模型组大鼠肺组织内TLR4、MUC5ac mRNA的相对表达量比正常组上升,观察组比模型组下降,差异均有统计学意义(P<0. 05)。结论:清金化痰汤对COPD大鼠肺组织内TLR4、MUC5ac表达有抑制作用,同时可降低BALF内炎性因子含量,改善其气道内粘液高分泌状态,降低气道内炎症程度。
Objective: To analyze the effect of Qingjin Huatan Decoction on airway inflammation and airway mucus hypersecretion for rats with chronic obstructive pulmonary disease(COPD). Methods: A total of 45 male Wistar male rats of SPF grade were randomly divided into three groups: normal group,model group and observation group. There were 15 rats in each group.The COPD model was prepared from the observation group and the model group. Four weeks after the successful modeling,the rats in the observation group were intragastrically administered with a dose of 2. 16g/kg Qingjin Huayu Decoction. The rats in the normal group and the model group were intragastrically administered with the same dose of normal saline once a day. Rat ventilator was used to detect forced vital capacity(FVC),peak expiratory flow rate(PEF) and forced expiratory volume(FEV0. 1) of0. 1s. ELISA was used to detect tumor necrosis factor-α in bronchoalveolar lavage fluid(BALF). The levels of(TNF-α),interleukin-17(IL-17) and interleukin-8(IL-8) were detected by Western blot. The expression of Toll-like receptor 4(TLR4) and MUC5 ac in lung tissue was detected by Western blot. Results: PFE,FEV0. 1and FVC in the model group and the observation group were lower than those in the normal group. The decrease in the observation group was lower than that in the model group,and the difference was statistically significant(P<0. 05). The contents of TNF-α,IL-17 and IL-8of the model group and the observation group were higher than those in the normal group. The increase of the observation group was lower than that of the model group,and the difference was statistically significant(P<0. 05). The expression of TLR4 and MUC5ac protein in the lung tissue of the model group rats. Compared with the normal group,the observation group decreased compared with the model group,and the difference was statistically significant(P<0. 05). The relative expression of TLR4 and MUC5ac mRNA in the lung tissue of the model group increased compared with the normal group,and the observation group decreased compared with the model group. The difference was statistically significant(P< 0. 05). Conclusion: Qingjin Huatan Decoction can inhibit the expression of TLR4 and MUC5ac in lung tissue of COPD rats,and can reduce the content of inflammatory factors in BALF,improve the high secretion of mucus in airway and reduce the degree of inflammation in airway.
Objective: To analyze the effect of Qingjin Huatan Decoction on airway inflammation and airway mucus hypersecretion for rats with chronic obstructive pulmonary disease(COPD). Methods: A total of 45 male Wistar male rats of SPF grade were randomly divided into three groups: normal group,model group and observation group. There were 15 rats in each group.The COPD model was prepared from the observation group and the model group. Four weeks after the successful modeling,the rats in the observation group were intragastrically administered with a dose of 2. 16g/kg Qingjin Huayu Decoction. The rats in the normal group and the model group were intragastrically administered with the same dose of normal saline once a day. Rat ventilator was used to detect forced vital capacity(FVC),peak expiratory flow rate(PEF) and forced expiratory volume(FEV0. 1) of0. 1s. ELISA was used to detect tumor necrosis factor-α in bronchoalveolar lavage fluid(BALF). The levels of(TNF-α),interleukin-17(IL-17) and interleukin-8(IL-8) were detected by Western blot. The expression of Toll-like receptor 4(TLR4) and MUC5 ac in lung tissue was detected by Western blot. Results: PFE,FEV0. 1and FVC in the model group and the observation group were lower than those in the normal group. The decrease in the observation group was lower than that in the model group,and the difference was statistically significant(P<0. 05). The contents of TNF-α,IL-17 and IL-8of the model group and the observation group were higher than those in the normal group. The increase of the observation group was lower than that of the model group,and the difference was statistically significant(P<0. 05). The expression of TLR4 and MUC5ac protein in the lung tissue of the model group rats. Compared with the normal group,the observation group decreased compared with the model group,and the difference was statistically significant(P<0. 05). The relative expression of TLR4 and MUC5ac mRNA in the lung tissue of the model group increased compared with the normal group,and the observation group decreased compared with the model group. The difference was statistically significant(P< 0. 05). Conclusion: Qingjin Huatan Decoction can inhibit the expression of TLR4 and MUC5ac in lung tissue of COPD rats,and can reduce the content of inflammatory factors in BALF,improve the high secretion of mucus in airway and reduce the degree of inflammation in airway.
引文
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[16]杨晓敏,赵娜妹,刘娟,等.健脾益肺化痰方通过抑制TNF-α信号通路改善COPD大鼠气道粘液高分泌的实验研究[J].天津中医药,2016,33(5):295~298
[2]蔡凌峰,王慧贤,林观康,等.痰热清注射液对慢性阻塞性肺疾病模型大鼠气道粘液高分泌的影响[J].成都医学院学报,2016,11(6):657~661
[3] Allinson J P,Hardy R,Donaldson G C,et al. The Presence of Chronic Mucus Hypersecretion across Adult Life in Relation to Chronic Obstructive Pulmonary Disease Development[J]. American Journal of Respiratory Critical Care Medicine,2016,193(6):662~665
[4]崔力沙,谌望孙,刘卓,等.慢性阻塞性肺疾病的气道粘液高分泌及其靶向治疗[J].医药导报,2017,36(1):55~57
[5]王骏,李春盈,刘治坤,等.慢性阻塞性肺疾病气道粘液高分泌大鼠模型的建立[J].心肺血管病杂志,2014,33(4):592~595
[6] Ha E V,Rogers D F. Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases[J]. Pharmacology,2016,97(12):84
[7]李战炜.三子养亲汤加味对慢性阻塞性肺疾病稳定期患者疗效、活动耐力及气道粘液高分泌的影响[J].中医学报,2018,7(4):214~218
[8]魏华生,吴波,胡筱,等.福多司坦对慢性阻塞性肺疾病急性加重期患者痰液粘蛋白5AC研究[J].中国实用内科杂志,2017,13(8):251~255
[9] Du W,Su J,Ye D,et al. Pinellia ternata Attenuates Mucus Secretion and Airway Inflammation after Inhaled Corticosteroid Withdrawal in COPD Rats[J]. American Journal of Chinese Medicine,2016,44(5):1027~1041
[10]杜建超,冯淬灵,葛东宇,等.清金化痰汤对慢性阻塞性肺疾病急性加重期模型大鼠肺组织Foxp3和RORγt表达的影响[J].北京中医药大学学报,2016,39(12):1006~1012
[11]徐晓红,邹丹凤,何湘军.气道吸痰专项护理对肺部感染性疾病伴气道粘液高分泌患者临床研究[J].山西医药杂志,2018,10(6):64~68
[12]曹继磊,程兆忠,孙妮娜,等. p38MAPK抑制剂对慢性阻塞性肺疾病大鼠气道粘液高分泌的影响[J].齐鲁医学杂志,2016,8(5):527~530
[13]孟玉凤,杜建超,冯淬灵,等.加味麻杏石甘汤治疗慢性阻塞性肺疾病急性加重的机制研究[J].北京中医药大学学报,2018,3(1):45~52
[14] Tsao C C,Tsao P N,Chen Y G,et al. Repeated Activation of Lung Invariant NKT Cells Results in Chronic Obstructive Pulmonary Disease-Like Symptoms[J]. Plos One,2016,11(1):7710~7715
[15]吴祎,钱风华,赵雷,等.健脾补肾法对慢性阻塞性肺疾病急性加重期患者气道粘液分泌和免疫功能的影响[J].实用临床医药杂志,2017,21(11):193~195
[16]杨晓敏,赵娜妹,刘娟,等.健脾益肺化痰方通过抑制TNF-α信号通路改善COPD大鼠气道粘液高分泌的实验研究[J].天津中医药,2016,33(5):295~298