慢支咳喘宁对慢性阻塞性肺疾病模型大鼠肺组织MMP-9和TIMP-1表达的影响

Effects of Manzhi Kechuanning Capsules on MMP-9 and TIMP-1 in lung tissue of rat models with chronic obstructive pulmonary disease

目的观察慢支咳喘宁胶囊对慢性阻塞性肺疾病(COPD)模型大鼠肺组织基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响,以探讨慢支咳喘宁胶囊在改善COPD气道重塑中的作用及其机制。方法将72只SPF级Wistar大鼠随机分为6组,即空白对照组,模型对照组,慢支咳喘宁低、中、高剂量组及桂龙咳喘宁组,空白对照组给予正常喂养,其余各组采用烟熏法加气管内注入脂多糖复制COPD大鼠模型,造模成功后,空白对照组及模型对照组灌胃给予生理盐水,其余各组分别灌胃给予低、中、高剂量慢支咳喘宁及桂龙咳喘宁,灌胃20 d后,测定各组大鼠肺功能,并用ELISA法测定各组大鼠肺组织中MMP-9及TIMP-1的含量。结果与空白对照组比较,模型对照组0.2 s用力呼气量(FEV0.2)、FEV0.2/FVC(用力肺活量)均显著减少,呼气阻力(Re)、吸气阻力(Ri)均显著增大,MMP-9,TIMP-1及MMP-9/TIMP-1比值显著升高,差异有统计意义(P<0.05);与模型对照组比较,各治疗组FEV0.2,FEV0.2/FVC均显著增多,Re,Ri均显著减小,MMP-9,TIMP-1及MMP-9/TIMP-1比值均显著降低,差异有统计意义(P<0.05),其中以慢支咳喘宁高剂量组及桂龙咳喘宁组改善最为显著(P<0.05)。结论慢支咳喘宁胶囊可有效抑制MMP-9和TIMP-1的生成,改善肺功能及细胞外基质(ECM)降解和沉积失衡,延缓气道重塑。

Objective To observe the effects of Manzhi Kechuanning Capsules on MMP-9 and TIMP-1 in lung tissue of rat models with chronic obstructive pulmonary disease（COPD）,and explore the effects and mechanism of Manzhi Kechuanning Capsules on improving the airway remodeling of COPD patients.Methods 72 SPF Wistar rats were randomly divided into six groups：normal control group,model control group,Manzhi Kechuanning low,medium and high dose group and Guilong Kechuanning group.The rats of normal control group were fed normally,the rest of rats were made the models of COPD by smoking method and endotracheal instillation of lipopolysaccharide（LPS）,after the models were made successfully,normal control group and model control group were given normal saline,the rest of the groups were given low,medium and high dose of Manzhi Kechuanning Capsules and Guilong Kechuanning Capsules.After administrating for 20 days,the lung function of rats were determined,and the contents of MMP-9 and TIMP-1 in lung tissue of rats were determined by ELISA method.Results Compared with normal control group,the FEV0.2,FEV0.2/FVC of model control group were significantly decreased and Re,Ri were significantly increased,and MMP-9,TIMP-1 and MMP-9/TIMP-1 were significantly increased（P0.05）.Compared with model control group,the FEV0.2,FEV0.2/FVC of all treating group were significantly increased and Re,Ri were significantly decreased,and MMP-9,TIMP-1 and MMP-9/TIMP-1 were significantly decreased（P0.05）,and the effects of Manzhi Kechuanning high dose group and Guilong Kechuanning group were most obvious（P0.05）.Conclusion Manzhi Kechuanning Capsules can effectively inhibit the expression of MMP-9 and TIMP-1,and can improve the lung function and ECM imbalance of degradation and sedimentary,delay airway remodeling.