姜辛夏颗粒对支气管哮喘大鼠肺组织基质金属蛋白酶及其抑制剂含量的影响

Effects of Jiangxinxia Granules on MMP-9 and TIMP-1 Levels in Lung of Bronchial Asthma Rats

目的观察姜辛夏颗粒对哮喘大鼠肺组织基质金属蛋白酶-9(MMP-9)及其抑制剂-1(TIMP-1)含量的影响,探讨该方对哮喘气道重建的机制。方法将52只雄性SD大鼠随机分为正常组、模型组、地塞米松组、姜辛夏颗粒组。通过皮下和腹腔注射0.2 mL抗原液及反复雾化吸入卵蛋白溶液建立哮喘气道重建动物模型。在哮喘激发2周后行肺组织HE染色观察并检测肺组织MMP-9、TIMP-1含量的变化。结果大鼠肺组织HE染色显示:模型组肺内支气管黏膜下可见大量炎细胞浸润,气道壁明显增厚,管壁周围及小血管周围有炎细胞浸润,上皮脱落,黏膜上皮增生活跃,管腔狭窄,基底膜及气道平滑肌层增厚明显,有部分肺泡壁变薄或断裂,融合成肺大泡;地塞米松组、姜辛夏颗粒组接近正常组,仅有轻度的炎症反应,与模型组相比,支气管及肺泡炎性浸润不明显,黏膜结构完整,肺泡间隔仅有部分断裂。模型组MMP-9和TIMP-1表达量明显增加,与正常组及地塞米松组和姜辛夏颗粒组比较差异有统计学意义(P<0.01);地塞米松组和姜辛夏颗粒组比较差异无统计学意义(P>0.05)。结论姜辛夏颗粒可明显改善哮喘大鼠的一般状况,改善肺组织病理变化,并能调节MMP-9和TIMP-1的表达,减轻气道炎症及气道重建的发生和发展,降低气道高反应性,从而发挥治疗哮喘的作用。

Objective To observe the effect of Jiangxinxia granules on MMP-9 and TIMP-1 levels in lung of asthma rat,and explore its mechanism in airway remodeling.Methods Fifty-two male SD rats were randomly divided into nornal group,model group,dexamethasone group and Jiangxinxia granules group.The asthmatic airway remodeling model was built by subcutaneous and intraperitoneal injection of 0.2 mL antigen solution as well as repeated inhalation of ovalbumin solution.The change of MMP-9 and TIMP-1 levels in lung was examined and lung tissue with HE stain was observed after two weeks of asthma stimulation.Results The lung tissue with HE stained showed：large number of inflammatory cell infiltration,significant thickening of airway wall,infiltration of inflammatory cells around vessel wall and small blood vessels,epithelial shedding,hyperplasia of mucosal epithelial,lumen stenosis,largely thickening of basement membrane and airway smooth muscle layer,as well as thinning or rupture of part of alveolar wall to integrate into bulla were observed on the intrapulmonary bronchial submucosal of model group.The changes of dexamethasone group and Jiangxinxia granules group were similar with the control group,except for mild inflammatory reaction.The inflammatory infiltration of bronchial and alveolar was not significant compared with the model group,furthermore,integrity of mucosal structural and part fracture of the alveolar septum were found.The expression of MMP-9 and TIMP-1 levels of the model group was highly increased,great significant difference was found compared with other groups（P0.01）.No significant difference was found between dexamethasone group and Jiangxinxia granules group（P0.05）.Conclusions Jiangxinxia granules may exert its effects on asthma through significantly improving the general condition and pathological changes in lung tissue,regulating the expression of MMP-9 and TIMP-1,reducing the airway inflammation and slowing the occurrence and development of airway remodeling,as well as decreasing the hyper-responsiveness of airway.