清肺渗湿汤对哮喘小鼠肺组织MMP-2、MMP-9、TIMP-1表达的影响  

Effects of Qingfei Shenshi Decoction on the expressions of MMP-2,MMP-9 and TIMP-1 in lung tissue of bronchial asthma mice

作　　者：徐晓晨 孙英 叶海燕 肖依 王坤 赵国静 胡海波 陆学超 Xiaochen Xu;Ying Sun;Haiyan Ye;Yi Xiao;Kun Wang;Guojing Zhao;Haibo Hu;Xuechao Lu(First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Department of Pulmonary Disease,Qingdao Hospital of Traditional Chinese Medicine,Qingdao 266033,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250014 [2]青岛市中医医院肺病科,青岛266033

出　　处：《国际中医中药杂志》2023年第6期709-713,共5页International Journal of Traditional Chinese Medicine

基　　金：山东中医药科技发展计划项目(2019-0596);青岛市2020年度医药科研指导计划(2020-WJD053)。

摘　　要：目的探究清肺渗湿汤对支气管哮喘小鼠肺组织MMP-2、MMP-9、金属蛋白酶组织抑制剂-1(TIMP-1)表达的影响。方法将50只BALB/C雄性小鼠按随机数字表法分为对照组、模型组、地塞米松组、清肺渗湿汤低剂量组、清肺渗湿汤高剂量组,每组10只。采用卵清蛋白激发法制备哮喘模型小鼠。造模成功后,地塞米松组灌胃地塞米松1.56 mg/kg,清肺渗湿汤低、高剂量组灌胃清肺渗湿汤14.235、28.470 g/kg,对照组、模型组灌胃等体积的0.9%氯化钠溶液。干预4周后,检测各组小鼠气道反应性(Penh值);HE染色观察肺组织病理学改变;ELISA检测肺泡灌洗液中IL-6、IL-1β、TNF-α水平;Western blot法检测肺组织中MMP-2、MMP-9、TIMP-1表达。结果与模型组比较,清肺渗湿汤各剂量组小鼠肺组织气管壁、肺泡壁损伤明显减轻。与模型组比较,清肺渗湿汤低、高剂量组小鼠Penh值降低(P<0.05),肺泡灌洗液中IL-6、IL-1β、TNF-α水平降低(P<0.05),肺组织MMP-9、MMP-2、TIMP-1表达降低(P<0.05),且具有一定的剂量依赖性。结论清肺渗湿汤可有效缓解哮喘模型小鼠气道炎症,减轻气道高反应性、改善肺功能,抑制气道重塑,其作用机制可能与下调MMP-2、MMP-9、TIMP-1表达有关。Objective To investigate the effects of Qingfei Shenshi Decoction on the expressions of matrix metalloproteinase-2(MMP-2)and MMP-9 and tissue inhibitor of metalloproteinase timps-1(TIMP-1)in lung tissue of asthma mice.Methods Totally 50 male BALB/C mice were divided into 5 groups:normal group,model group,dexamethasone group,Qingfei Shenshi Decoction low-and high-dosage groups(10 mice/group)according to random number table method.Asthma model mice were prepared by ovalbumin(OVA)challenge method.After successful modeling,the dexamethasone group was given dexamethasone for gavage at the rate of 1.56 mg/kg,while Qingfei Shenshi Decoction groups were given high and low doses of Qingfei Shenshi Decoction for gavage at the rate of 14.235 g/kg and 28.470 g/kg,respectively.Normal group and model group were given 0.9%sodium chloride solution by gavage.At the end of gavage administration for 4 weeks,the airway reactivity(Penh value)in each group was detected;HE staining was used to observe the pathological changes of lung tissue;the contents of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid were determined by enzyme Linked immunosorbent assay(ELISA);the expressions of MMP-2,MMP-9 and TIMP-1 in lung tissue were detected by Western-blot.Results Compared with model group,the damage of airway wall and alveolar wall of lung tissue in Qingfei Shenshi Decoction groups was significantly reduced.Compared with model group,the Penh value,IL-6,IL-1βand TNF-αlevels in Qingfei Shenshi Decoction low-and high-dosage groups decreased(P<0.05),and the expressions of MMP-9,MMP-2 and TIMP-1 in lung tissue decreased(P<0.05),with a certain dose dependence.Conclusion Qingfei Shenshi Decoction can effectively alleviate airway inflammation,reduce airway hyperresponsiveness,improve lung function and inhibit airway remodeling in asthmatic mice.Its mechanism may be related to down-regulating the expressions of MMP-2,MMP-9 and TIMP-1.

关 键 词：哮喘 清肺渗湿汤 炎症 肺功能 气道重塑 基质金属蛋白酶 小鼠 

分 类 号：R285.5[医药卫生—中药学]