辛伐他汀对慢性阻塞性肺疾病大鼠基质金属蛋白酶及炎症因子表达的影响  

The Effects of Simvastatin on Expression of Matrix Metalloproteinase and Inflammatory Factors in COPD Rats

作　　者：熊萍[1] 黄炎明[1] 左万里[1] 张春来[1] 周伟[2] 

机构地区：[1]江门市中心医院呼吸科,广东江门529030 [2]江门市中心医院病理科,广东江门529030

出　　处：《中国呼吸与危重监护杂志》2015年第6期541-545,共5页Chinese Journal of Respiratory and Critical Care Medicine

摘　　要：目的探讨辛伐他汀早期干预对慢性阻塞性肺疾病(简称慢阻肺)大鼠基质金属蛋白酶(MMP)及炎症因子表达的影响。方法 40只雄性Wistar大鼠随机均分为正常组(A组)、辛伐他汀组(B组)、慢阻肺模型组(C组)及辛伐他汀干预组(D组)。C组和D组采用反复香烟烟雾暴露法制备慢阻肺模型。B组和D组大鼠采用辛伐他汀5 mg·kg^(-1)·d^(-1)灌胃,其他两组用等体积的生理盐水灌胃,共16周。造模结束后进行大鼠肺功能检测及肺组织病理学观察。用酶联免疫吸附试验(ELISA)测定肺组织匀浆中MMP-2、MMP-9、白细胞介素6(IL-6)、IL-8及肿瘤坏死因子α(TNF-α)的含量。结果 C组大鼠的气道内阻力[(0.813±0.019)cm H_2O·s^(-1)·L^(-1)]和D组大鼠气道内阻力[(0.622±0.012)cm H_2O·s^(-1)·L^(-1)]显著高于A组[(0.402±0.021)cm H_2O·s^(-1)·L^(-1)]和B组[(0.417±0.019)cm H_2O·s^(-1)·L^(-1)](P<0.01)。但D组大鼠气道内阻力低于C组(P<0.01)。A组和B组大鼠气道内阻力差异无统计学意义(P>0.05)。C组大鼠肺组织病理切片的支气管炎症及肺气肿程度均较D组明显,A组和B组大鼠未见支气管炎症及肺气肿改变。ELISA检测结果显示:C组大鼠肺组织匀浆中MMP-2[(0.226±0.008)ng/m L]及MMP-9[(1.441±0.059)ng/m L]的含量较D组MMP-2[(0.174±0.007)ng/m L]及MMP-9[(1.094±0.047)ng/m L]的含量升高(P<0.01)。C组大鼠肺组织匀浆中IL-6[(44.59±1.91)pg/m L]、IL-8[(84.30±6.56)pg/m L]及TNF-α[(40.75±1.55)pg/m L]的含量较D组IL-6[(36.14±1.41)pg/m L]、IL-8[(58.17±6.28)pg/m L]及TNF-α[(34.42±1.83)pg/m L]的含量均增高(P<0.01)。结论辛伐他汀对慢阻肺者的肺部炎症有抑制作用,可降低肺内MMP及炎症因子的表达。Objective To explore the effects of simvastatin on the expression of matrix metalloproteinase（ MMP） and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease（ COPD）. Methods 40 male Wistar rats were randomly divided into four groups,including a normal group（ group A）,a simvastatin group（ group B）,a COPD model group（ group C） and a simvastatin intervention group（ group D）. The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time,the rats of group B and D were given by gavage 5 mg /（ kg·d） with simvastatin,and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay（ ELISA） method was used to measure the content of MMP-2,MMP-9,IL-6,IL-8,TNF-α in lung tissue homogenate. Results The airway resistance of group C and group D was significantly higher than the group A and group B（ P〈0. 01）,and the airway resistance of group D was significantly lower than group C（ P〈0. 01）. The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2,MMP-9,IL-6,IL-8,TNF-α in group C were all significantly higher than those in group D.Conclusion Simvastatin has inhibitory effect on pulmonary inflammation of COPD,and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.

关 键 词：慢性阻塞性肺疾病 基质金属蛋白酶 炎症因子 辛伐他汀 

分 类 号：R563.9[医药卫生—呼吸系统]