咳喘宁对支气管哮喘大鼠气道重塑及MMP-9、TIMP-1的影响

目的 观察咳喘宁对支气管哮喘大鼠气道形态学和基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶组织抑制剂-1（TIMP-1）的影响.方法 40只SD大鼠随机分为正常组、模型组、咳喘宁高、低剂量组（27 和13.5 g生药/kg体重）、桂龙咳喘宁胶囊对照组（0.41 g/kg体重）,每组8只.除正常组外以卵蛋白致敏并吸入激发法制备大鼠支气管哮喘模型,各治疗组均从第1次哮喘激发开始（造模第3周）至处死前每天灌胃给药,激发并给药4 w后处死大鼠,取肺组织HE染色,彩色图像分析仪测量支气管管壁厚度、平滑肌厚度,采用ELISA双抗体夹心法测定肺组织MMP-9、TIMP-1含量.结果 与正常组比较,模型组大鼠支气管管壁和平滑肌厚度、肺组织MMP-9、TIMP-1含量及二者比值明显增加（P＜0.01）;与模型组比较,各治疗组均可显著降低支气管管壁和平滑肌厚度（P＜0.01）,降低肺组织MMP-9、TIMP-1含量以及二者比值（P＜0.05或P＜0.01）;且咳喘宁高、低剂量组优于桂龙咳喘宁胶囊组（P＜0.05或P＜0.01）.结论咳喘宁可通过降低肺组织MMP-9和TIMP-1含量,调节二者比值,抑制支气管哮喘大鼠气道壁增厚和平滑肌增生肥大,从而抑制支气管哮喘大鼠气道重塑.

Effect of Kechuanning on MMP-9,TIMP-1 and airway remolding of bronchial asthmatic rats

Objective To observe effect of Kechuanning on MMP-9,TIMP-1 and airway remolding of bronchial asthmatic rats.Methods 40 SD rats were randomly divided into normal group,model group,Kechuanning high-and low-dose group (27,13.5 g/kg),Guilongkechuanning control group (0.41 g/kg),8 rats each group.The bronchial asthmatic model was established by egg protein sensibilization and long-term inhalation provocation.The rats of each treatment groups were lavaged each day from the first time of provocation to execution.After 4 weeks of treatment,the rats were killed to obtain lung tissue for dyeing of HE.A computer assisted image analysis system was used to determine the thickness change of bronchus wall and smooth muscle.The contents of MMP-9 and TIMP-1 in lung tissue were determined by ELISA double antibody sandwich method.Results The thickness of bronchus wall and bronchus smooth muscle,the content and the relative value of MMP-9 and TIMP-1 in lung tissue were increased in model group than those in normal group (P<0.01);the thickness of bronchus wall and bronchus smooth muscle,the content and the relative value of MMP-9 and TIMP-1 in lung tissue were decreased (P<0.01)in the each treatment group (P<0.05 or P<0.01)than those in model group;The high-and low-dose group surpassed Kechuanning group (P<0.05 or P<0.01).Conclusions Kechuanning could decrease the product of MMP-9,TIMP-1 in lung tissue and regulate the relative value of both to inhibit air passage thickening and smooth muscle hyperplasia to restrain airway remolding.