小儿止咳颗粒对哮喘大鼠气道重塑影响的实验研究  

Experiment Research of Effect of Xiaoerzhike Granules on Airway Remodeling of Asthmatic Rats

作　　者：郑艳萍[1] 刘映玲[1] 黄慧芳[1] 郑敏[1] 许双虹[1] 赖意芬[1] 

机构地区：[1]深圳市中医院儿科,深圳518033

出　　处：《新中医》2016年第7期282-286,共5页New Chinese Medicine

基　　金：深圳市科技创新委员会项目(JCYJ20140408153413103)

摘　　要：目的:观察小儿止咳颗粒对哮喘模型大鼠血清及肺组织中基质金属蛋白酶(MMP-9)、基质金属蛋白酶组织抑制因子(TIMP-1)的表达,以及对肺组织形态学变化的影响,探讨其对咳嗽变异性哮喘气道重塑的作用。方法:36只SD雌性大鼠随机分为空白对照组、病理模型组、地塞米松组、小儿止咳颗粒低、中、高剂量组,每组6只。除空白对照组外,其他各组分别于第1天、第8天腹腔注射新鲜配制的鸡卵白蛋白(OVA)氢氧化铝悬液。第15天上午病理模型组以10 m L/kg生理盐水灌胃,地塞米松组以0.3 mg/kg地塞米松灌胃,小儿止咳颗粒低、中、高剂量组分别以12.5 g/kg、25 g/kg、50 g/kg小儿止咳颗粒溶液灌胃,每天1次,共给药40天。药物干预2小时后,行鸡卵白蛋白溶液雾化吸入30min激发哮喘(空白对照组使用生理盐水),连续4周,每天1次。治疗结束后收集血清、肺组织。检测血清MMP-9、TIMP-1含量;免疫组织化学法检测肺组织中MMP-9、TIMP-1表达;HE染色观察肺组织的病理形态;Masson染色观察肺组织中胶原纤维的沉积程度。结果:与空白对照组比较,病理模型组大鼠的血清MMP-9与TIMP-1水平均明显升高(P<0.01),提示哮喘大鼠造模成功;与病理模型组比较,地塞米松组以及小儿止咳颗粒低、中、高剂量组中血清MMP-9和TIMP-1水平显著降低(P<0.05)。在肺组织形态学方面,病理模型组气道壁明显增厚,肺泡间隔不均匀增厚、增宽,气管黏膜皱璧增多,肺泡壁明显增厚、充血,气管及血管周围可见灶状炎性细胞浸润,可见轻-中度肺气肿,毛细血管及细支气管周边可见较多胶原纤维沉积,小儿止咳颗粒干预后上述病理表现得到改善,高剂量的小儿止咳颗粒疗效优于地塞米松。结论:小儿止咳颗粒下调MMP-9与TIMP-1的表达,减少ECM在气道的沉积,改善气道炎症,从而逆转气道重塑,达到治疗哮喘的目的。Objective： To observe the effect of Xiaoerzhike granules on expression of matrix metalloproteinase（MMP- 9）and tissue inhibitors of matris metalloproteinase（TIMP- 1） in asthmatic rats serum and lung tissue,meanwhile on lung tissue morphological changes,and to discuss its effect on cough variant asthma（CVA）airway remodeling. Methods：Thirty- six cases of female rats were divided into blank control group,pathological model group,hexadecadrol group,low,mid and high dose of Xiaoerzhike granules group,6 cases in each group. All groups except blank control group,were intraperitoneally injected by chicken ovalbumin（OVA） aluminum hydroxide suspension on the 1st day and 8th day respectively. On the morning of 15 th day,the pathological model group was given 10 m L/kg normal saline gavage, hexadecadrol group was given 0.3 mg/kg hexadecadrol gavage,low,mid and high dose of Xiaoerzhike granules group were given gavage respectively of 12.5 g/kg,25g/kg and 50 g/kg of Xiaoerzhike granules solution, one time a day, for 40 days. After 2 hours of drug intervention,atomization inhaled chicken ovalbumin solution for 30 min to induce asthma（normal saline was used in blank control group）,one time a day,for 4 consecutive weeks. Collected serum and lung tissue after treatment. Detected levels of MMP- 9 and TIMP- 1 in serum;detected expressions of MMP- 9 and TIMP- 1 in lung tissue by immunohistochemical method;observed pathomorphism of lung tissue by HE dying,and deposit level of collagenous fiber in lung tissue by Masson dying. Results：Comparing with blank control group,the levels of MMP- 9 and TIMP- 1 in serum were increased obviously in pathological model group（P〈0.01）,which means asthmatic rats models were established successfully. Comparing with pathological model group,the levels of MMP- 9 and TIMP- 1 in hexadecadrol group,low,mid and high dose of Xiaoerzhike granules group were all decreased obviously（P〈0.05）. In terms of lung histomorphology,port wall in model group thickened obviously,alveolar

关 键 词：哮喘 气道重塑 小儿止咳颗粒 血清基质金属蛋白酶(MMP-9) 血清基质金属蛋白酶组织抑制因子(TIMP-1) 动物实验 大鼠 

分 类 号：R285.5[医药卫生—中药学]