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 H2O·s-1·L-1]和D组大鼠气道内阻力[(0.622±0.012) cm H2O·s-1·L-1]显著高于A组[(0.402±0.021) cm H2O·s-1·L-1]和B组[(0.417±0.019) cm H2O·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/mL]及MMP-9[(1.441±0.059) ng/mL]的含量较D组MMP-2[(0.174±0.007) ng/mL]及MMP-9[(1.094±0.047) ng/mL]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/mL]、IL-8[(84.30±6.56) pg/mL]及TNF-α[(40.75±1.55) pg/mL]的含量较D组IL-6[(36.14±1.41) pg/mL]、IL-8[(58.17±6.28) pg/mL]及TNF-α[(34.42±1.83) pg/mL]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
References
[1]
1. ？Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease:GOLD executive summary. Am J Respir Crit Care Med,2007,176:532-555.
3. Larsson K. Inflammatory markers in COPD. Clin Respir J,2008,2 Suppl 1:84-87.
[4]
4. Keatings VM, Collins PD, Scott DM, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med,1996,153:530-534.
[5]
5. Kuschner WG, D'Alessandro A, Wong H, et al. Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J,1996,9:1989-1994.
[6]
6. Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet,2011,378:1015-1026.
8. Omachi TA, Eisner MD, Rames A, et al. Matrix metalloproteinase-9 predicts pulmonary status declines in alpha1-antitrypsin deficiency. Respir Res,2011,12:35.
[9]
9. Culpitt SV, Rogers DF, Traves SL, et al. Sputum matrix metalloproteases:comparison between chronic obstructive pulmonary disease and asthma. Respir Med,2005,99:703-710.
[10]
10. Louhelainen N, Stark H, Mazur W, et al. Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation:a research study. BMC Pulm Med,2010,10:13.
[11]
11. Navratilova Z, Zatloukal J, Kriegova E, et al. Simultaneous up-regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic obstructive pulmonary disease. Respirology,2012,17:1006-1012.
[12]
12. Hothersall EC, McSharry C, Thomson NC. Potential therapeutic role for statins in respiratory disease. Thorax,2006,61:729-734.
[13]
13. Wright JL, Zhou S, Preobrazhenska O, et al. Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling. Am J Respir Crit Care Med,2011,183:50-58.
