布地奈德联合辛伐他汀对COPD大鼠肺组织NE及YKL-40表达的影响

Effect of budesonide combined with simvastatin on the expression of NE and YKL-40 in lung tissues of COPD rats

目的观察布地奈德联合辛伐他汀对COPD(慢性阻塞性肺疾病,Chronic obstructive pulmonary disease)大鼠肺组织NE(中性粒细胞弹性蛋白酶,Neutrophil elastase)及YKL-40(软骨蛋白39,Cartilage protein39)表达的影响。方法选择200只SPF(无特定病原体级,specific pathogen free)级大鼠,按随机数字分为4组,即M组(模型组,model group)、BD组(布地奈德组,budesonide group)、SV组(辛伐他汀组,simvastatin group)、BD+SV组(布地奈德联合辛伐他汀组,budesonide combined simvastatin group),各50只。M组大鼠按照模型建立COPD小鼠的模型,其余三组分别进行不同的干预方案。12周后观察4组大鼠的体质量、血清炎性介质、肺组织的病理改变以及肺组织中的NE、YKL-40的表达水平。结果 BD组、SV组以及BD+SV组的大鼠体质量存在均匀增加趋势,M组大鼠体质量增加幅度显著低于同时间段的BD组、SV组以及BD+SV组的大鼠,4组大鼠体质量在组间、时点间、组间-时点间的比较差异较大,差异有统计学意义(P <0. 05);各组大鼠的血清炎症因子IL-6(白细胞介素6,Interleukin 6)、IL-8(白细胞介素8,Interleukin 8)、TNF-α(肿瘤坏死因子α,tumor necrosis factor-α)相比,差异有统计学意义(P <0. 05),各组的LTB4(白三烯B4,Leukotriene B4)之间差异不大,无统计学意义(P> 0. 05);与M组相比,其余三组的病理半定量评分均显著下降,差异有统计学意义(P <0. 05),BD组、SV组、BD+SV组之间进行两两比较,病理半定量评分差异不大,差异无统计学意义(P> 0. 05);其余三组与M组相比,NE显著减少,差异有统计学意义(P <0. 05); M组的YKL-40显著高于其余三组,差异较大,有统计学意义(P <0. 05)。结论布地奈德联合辛伐他汀能够有效地降低COPD大鼠的全身炎症、气道炎症反应,改善肺组织的病理。

Objective To observe the effect of budesonide combined with simvastatin on the expression of NE （Neutrophil elastase） and YKL-40 （Cartilage protein 39） in lung tissues of COPD rats. Methods 200 SPF （specific pathogen free） rats were randomly divided into 4 groups, the M group （the model group）, the BD group （the budesonide group）, the SV group （the simvastatin group）, and the BD＋SV group （the budesonide combined with simvastatin group）, 50 cases in each group. The group M was established according to the model of COPD mice, and the other three groups were given different intervention programs. After 12 weeks, their body weight, serum inflammatory mediators, pathological changes of lung tissue and the expression levels of NE and YKL-40 in lung tissues were observed in the 4 groups. Results The mass of rats in the group BD, the group SV and the group BD＋SV increased evenly, and the increase in the group M was significantly lower than that in the group BD, the SV group and the BD＋SV group. There was significant difference in body mass between any two groups （ P〈 0.05）. There were significant differences in serum inflammatory factors IL-6, IL-8 and TNF-α between any two groups （ P〈 0.05）, but there was no significant difference in LTB4 （ P〉 0.05）. Compared with the group M, semi quantitative pathological scores of the rest three groups deceased significantly （ P〈 0.05）. There was no significant difference in pathological semi quantitative score between the group BD, the group SV and the group BD＋SV （ P〉 0.05）. Compared with the M group, the value of NE in the rest three groups decreased significantly （ P〈 0.05）. The level of YKL-40 was significantly higher in the group N than in the other three groups （ P〈 0.05）. Conclusion Budesonide combined with simvastatin can effectively reduce systemic inflammation and airway inflammation in COPD rats, and improve the pathology of lung tissue.