泼尼松治疗慢性阻塞性肺疾病大鼠的效果及对基质金属蛋白酶家族蛋白的调控作用

The effect of prednison on chronic obstructive pulmonary disease and the regulation on metalloproteinase proteins

目的分析泼尼松治疗慢性阻塞性肺疾病大鼠的效果及对基质金属蛋白酶家族蛋白的调控作用,为临床治疗提供参考。方法 SD大鼠随机分为5组:对照组、模型组、泼尼松低剂量治疗组、泼尼松中剂量治疗组和泼尼松高剂量治疗组(n=8)。除对照组大鼠外,其余各组大鼠给予鼻腔滴入肺炎克雷伯菌悬液,浓度控制在6×108CFU/ml,每5d处理一次,持续8周。香烟烟雾吸入每次使用8支,分两次燃烧。泼尼松治疗组大鼠给予对应剂量的泼尼松(1 mg/kg,10 mg/kg,50 mg/kg)治疗,其余各组给予生理盐水。分析泼尼松的治疗效果及治疗后大鼠体内基质金属蛋白酶(MMP)、基质金属蛋白酶抑制剂(TIMP)和炎症因子水平的变化。结果慢性阻塞性肺疾病大鼠潮气量、呼气峰流速及50%潮气量呼气流量水平均明显降低,而基质金属蛋白酶MMP1、MMP2及MMP6和抑制剂TIMP1、TIMP2、TIMP8及白细胞介素、AP1和CXCR4蛋白水平均明显升高,且与对照组相比差异有显著统计意义(P<0.05),而经泼尼松治疗后模型组大鼠的上述异常得到明显的改善(P<0.05),且呈剂量依赖性。结论泼尼松治疗慢性阻塞性肺疾病大鼠的效果与其调控体内基质金属蛋白酶家族和炎症因子水平有关。

Objective The present research aimed to explore the effect of prednison on chronic obstructive pulmonary disease and the reg-ulation on metalloproteinase proteins. Methods SD rats were divided into 5 groups,control group,model group,prednison at low,middle and high dose（n = 8）. Chronic obstructive pulmonary disease rats were duplicated by the treatment of smudging combined bacterial infection（6 × 10^8 CFU/ ml）. The pulmonary function and expression of serum metalloproteinase and its inhibitors were detected after prenidson treatment at different dose（1 mg/ kg,10 mg/ kg,50 mg/ kg）. Control and model group rats received natural saline treatment. The expression of MMP,TIMP,AP1, CXCR4 and interleukins were assayed. Results The pulmonary function of model rats were normalized greatly（ P ﹤ 0. 05）after the medication of predison. The results also showed that the serum content of MMP1,MMP2,MMP6,TIMP1,TIMP2 and AP1 as well as CXCR4 were decreased significantly（ P ﹤ 0. 05）after the medication of predison. At the same time,the interleukins including IL - 1,IL - 2,IL - 3 and IL - 6 were in-hibited（ P ﹤ 0. 05）in model rats after drug medication,and dose - dependent manner. Conclusion Predison alleviate the abnormal pulmonary function maybe related with the regulation of metalloproteinase and its inhibitors.