慢性阻塞性肺疾病模型大鼠肺组织基质金属蛋白酶9及组织金属蛋白酶抑制剂1与固本颗粒胶囊

背景:中医药防治慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的有效性和安全性已初步得到临床认证。 目的：观察COPD模型大鼠肺组织中基质金属蛋白酶9及其特异性抑制物组织金属蛋白酶抑制剂1表达与固本颗粒胶囊干预的影响。方法：将50只Wistar大鼠随机等分为5组,除正常组外,其余大鼠均以烟熏及气管内滴注脂多糖的方式建立COPD模型。造模   29 d,泼尼松组、固本颗粒胶囊低、高剂量组分别灌胃给予醋酸泼尼松            1.04 mg/(kg•d),固本颗粒胶囊0.47,0.94 g/(kg•d),1次/d,观察记录大鼠的一般状况。免疫组织化学方法检测大鼠肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达。结果与结论：COPD大鼠肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达显著增强(P < 0.05)。药物干预后,COPD大鼠的一般状况明显改善,肺组织中基质金属蛋白酶9及组织金属蛋白酶抑制剂1的表达有所降低;其中,醋酸泼尼松的作用最为显著,固本颗粒高剂量次之,低剂量最弱。说明固本颗粒胶囊能以剂量依赖的方式缓解COPD大鼠的临床表现,改善气道重塑,纠正COPD大鼠体内蛋白酶和抗蛋白酶失衡。

Effects of Gubenkeli capsule on matrix metallopeptidase 9 and tissue inhibitor of metalloproteinase1 levels in lung tissue of a rat model of chronic obstructive pulmonary disease

BACKGROUND:The effectiveness and safety of traditional Chinese medicine treatment for chronic obstructive pulmonary disease (COPD) have been preliminarily approved by clinical practices.OBJECTIVE:To investigate the effects of Gubenkeli capsule on the protein expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase1 (TIMP-1) in lung tissue of COPD model rats.METHODS:A total of 50 Wistar rats were randomly divided into five groups with 10 rats in each group: normal control, model, prednisone, Gubenkeli capsule-low dose, and Gubenkeli capsule-high dose. COPD rat models were established in all rats with the exception of the normal control rats by smoking and intratracheal instillation of LPS. At 29 days after COPD induction, rats from the prednisone, Gubenkeli capsule-low dose, Gubenkeli capsule-high dose groups were intragastrically administered prednisone (1.04 mg/kg per day), Gubenkeli capsule (0.4, 0.94 g/kg per day), once a day, to observer rat general conditions. Protein expression of MMP-9 and TIMP-1 in the lung tissue was detected by immunohistochemical methods.  RESULTS AND CONCLUSION:Protein expression of MMP-9 and TIMP-1 in the lung tissue of COPD rats was significantly increased (P < 0.05). After drug intervention, the general conditions of COPD rats were greatly improved, and protein expression of MMP-9 and TIMP-1 in the lung tissue was decreased. Prednisone yields the strongest effects, followed by high-dose Gubenkeli capsule and low-dose Gubenkeli capsule. These findings demonstrate that Gubenkeli capsule alleviates the clinical manifestations of COPD model rats, improve airway remodeling, and correct the imbalance between prolease and antiprotease in a dose-response manner.