肺心宁汤对慢性阻塞性肺疾病模型大鼠基质金属蛋白酶9及基质金属蛋白酶抑制剂1水平的影响

Effect of Feixinning Decoction on the levels of MMP-9 and TIMP-1 in rats with COPD

目的观察肺心宁汤对慢性阻塞性肺疾病(COPD)模型大鼠基质金属蛋白酶9(MMP-9)及基质金属蛋白酶抑制剂1(TIMP-1)水平的影响,探讨其治疗COPD的作用机制。方法将60只Wistar大鼠随机分为正常组、模型组、醋酸泼尼松组、肺心宁汤低剂量组、肺心宁汤中剂量组及肺心宁汤高剂量组,每组10只。除正常组外,其余各组大鼠采用烟熏联合气道内滴入脂多糖的方法建立COPD模型。造模成功后,正常组及模型组按6.3 mL/kg予蒸馏水灌胃,醋酸泼尼松组按0.027 g/kg予醋酸泼尼松片药液灌胃,肺心宁汤低、中、高剂量组分别按3.3、6.6、13.2 mL/kg予肺心宁汤药液(生药含量0.525 g/mL)灌胃,每日1次,连续灌胃28 d。比较各组灌胃后血清MMP-9、TIMP-1水平及肺组织中MMP-9 mRNA、TIMP-1 mRNA表达情况。结果与正常组比较,模型组大鼠血清MMP-9水平明显升高(P<0.05),TIMP-1水平明显降低(P<0.05);与模型组比较,醋酸泼尼松组及肺心宁汤低、中、高剂量组血清MMP-9水平均明显降低(P<0.05),TIMP-1水平均明显升高(P<0.05);肺心宁汤各剂量组组间比较,肺心宁汤中、高剂量组血清MMP-9水平均明显低于肺心宁汤低剂量组(P<0.05),TIMP-1水平均明显高于肺心宁汤低剂量组(P<0.05),且肺心宁汤高剂量组对血清MMP-9及TIMP-1水平改善均优于肺心宁汤中剂量组(P<0.05)。与正常组比较,模型组大鼠肺组织MMP-9 mRNA表达明显升高(P<0.05),TIMP-1 mRNA表达明显降低(P<0.05);与模型组比较,醋酸泼尼松组及肺心宁汤低、中、高剂量组肺组织MMP-9 mRNA表达均明显降低(P<0.05),TIMP-1 mRNA表达均明显升高(P<0.05);肺心宁汤各剂量组组间比较,肺心宁汤中、高剂量组肺组织MMP-9 mRNA表达均明显低于肺心宁汤低剂量组(P<0.05),TIMP-1 mRNA表达均明显高于肺心宁汤低剂量组(P<0.05),且肺心宁汤高剂量组对肺组织MMP-9 mRNA及TIMP-1 mRNA表达改善均优于肺心宁汤中剂量组(P<0.05)。结论肺心宁汤对于COPD大鼠具有确切的治疗作用,其作用机制可能与降低血清MMP-9水平,升高TIMP-1水平,抑制肺组织MMP-9 mRNA表达,促进TIMP-1 mRNA表达,进而干预气道重塑过程,改善肺组织病理损伤,延缓病情进展,且其对COPD的改善作用与剂量呈正相关。

Objective To observe the effect of Feixinning Decoction on the levels of matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in rats with chronic obstructive pulmonary disease(COPD),and to explore its mechanism of action in the treatment of COPD.Methods Sixty Wistar rats were randomly divided into normal group,model group,prednisone acetate group,low-dose Feixinning Decoction group,medium-dose Feixinning Decoction group and high-dose Feixinning Decoction group,with 10 rats in each group.Except for the normal group,the COPD model was established by the method of smoking combined with intratracheal instillation of lipopolysaccharide.After successful modeling,the normal group and model group were given distilled water by gavage at the rate of 6.3 mL/kg,the prednisone acetate group was given Prednisone Acetate Tablets by gavage at the rate of 0.027 g/kg,and the low-,medium-,and high-dose Feixinning Decoction groups were given Feixinning Decoction(drug content 0.525 g/mL)by gavage at the rate of 3.3,6.6,and 13.2 mL/kg respectively,once a day for 28 consecutive days.The levels of MMP-9 and TIMP-1 in serum and the expressions of MMP-9 mRNA and TIMP-1 mRNA in lung tissue were compared.Results Compared with the model group,the serum level of MMP-9 in the model group was significantly higher(P<0.05),and the TIMP-1 level decreased significantly(P<0.05).Compared with themodel group,the serum MMP-9 levels in prednisone acetate group and Feixinning low,medium and high dose groups were significantly lower(P<0.05).TIMP-1 levels were significantly increased(P<0.05).The levels of serum MMP-9 in the middle and high-dose groups of Feixining decoction were significantly lower than those in the low-dose group of Feixinning decoction(P<0.05).TIMP-1 levels were significantly higher than those in low-dose Feixinning Decoction group(P<0.05).The improvement of serum MMP-9 and TIMP-1 levels in Feixinning Decoction high-dose group was better than that in Feixinning Decoction medium-dose group(P<0.05).Compared with the normal group,the serum level of MMP-9 mRNA in the model group was significantly higher(P<0.05),and the TIMP-1 mRNA level decreased significantly(P<0.05).Compared with themodel group,the serum MMP-9 mRNA levels in prednisone acetate group and Feixinning low,medium and high dose groups were significantly lower(P<0.05).TIMP-1 mRNA levels were significantly increased(P<0.05).The levels of serum MMP-9 mRNA in the middle and high-dose groups of Feixining decoction were significantly lower than those in the low-dose group of Feixinning decoction(P<0.05).TIMP-1 mRNA levels were significantly higher than those in low-dose Feixinning Decoction group(P<0.05).The improvement of serum MMP-9 mRNA and TIMP-1 mRNA levels in Feixinning Decoction high-dose group was better than that in Feixinning Decoction medium-dose group(P<0.05).Conclusion Feixining decoction has definite therapeutic effect on COPD rats.Maybe its mechanism of action is to reduce the level of serum MMP-9,increase the level of TIMP-1,inhibit the expression of MMP-9 mRNA in lung tissue,promote the expression of TIMP-1 mRNA,and then intervene in the process of airway remodeling,improve the pathological injury of lung tissue,and delay the progress of the disease.Moreover,the improvement effect of the decoction on COPD is positively correlated with the dose.