title: [Effects of simvastatin on airway inflammation and airway mucus hypersecretion in rats with chronic obstructive pulmonary disease].
abstract: OBJECTIVE
  To explore the preventive and therapeutic effects of simvastatin on rats with chronic obstructive pulmonary disease (COPD) and examine the mechanism of airway inflammation and airway mucus hypersecretion.
  
  
  METHODS
  The rat model of COPD was established by cigarette smoking and an intratracheal injection of lipopolysaccharide (LPS). A total of 18 male Sprague-Dawley rats were randomly divided into control, COPD and simvastatin groups (n=6 each). The control and COPD groups received normal saline once daily via intragastric administration (i.g.) while the simvastatin group had simvastatin (0.5 g/L) 1 ml/100 g once daily via i.g. Pulmonary function was tested and pathological changes in bronchus and lung were observed. The bronchoalveolar lavage fluid (BALF) levels of interleukin-8 (IL-8), interleukin-17 (IL-17) and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of intercellular adhesion molecule 1 (ICAM-1), nuclear factor κB (NF-κB), mucin 5AC (MUC5AC) and Toll-like receptor 4 (TLR4) in rat airway were detected by immunohistochemical staining. The mRNA and protein expressions of TLR4 and MUC5AC in bronchi and lung tissue were detected by fluorescent real time quantitative polymerase chain reaction (RT-PCR) and Western blot.
  
  
  RESULTS
  The changes of bronchi and lung tissues in COPD group were consistent with typical pathological manifestations of COPD. As compared with the COPD group, the degree of pulmonary pathological damage and the decline of pulmonary function in the simvastatin group were significantly lessened, but still remarkable as compared with the control group. The BALF levels of IL-8, IL-17 and TNF-α in the smvastatin group [(484.4 ± 11.1), (78.9 ± 2.0), (192.7 ± 2.0) ng/L] were significantly lower than those in the COPD group [(605 ± 48.7), (89.9 ± 6.9), (212.6 ± 10.7) ng/L], but still higher than those in the control group [(341.2 ± 21.4), (56.0 ± 2.9), (127.5 ± 9.0) ng/L respectively] (all P <0.01). Compared with COPD group, the expression levels of ICAM-1, NF-κB, MUC5AC and TLR4 protein were significantly lower in the simvastatin group, but still higher than the control group (all P <0.01). Furthermore, the expression levels of mRNA and protein of MUC5AC and TLR4 were significantly lower in the simvastatin group than those in the COPD group (all P <0.05).
  
  
  CONCLUSIONS
  In COPD model rats, simvastatin can decrease the levels of IL-8, IL-17 and TNF-α in BALF and inhibit the expression levels of ICAM-1, NF-κB, MUC5AC and TLR4 protein in airway and lung tissue. Thus it plays preventive and therapeutic roles by reducing airway inflammation and airway mucus hypersecretion.
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China; Email: ahzyws@163.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Chundong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001980:Bronchi; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D008168:Lung; D008297:Male; D055271:Mucin 5AC; D009093:Mucus; D016328:NF-kappa B; D029424:Pulmonary Disease, Chronic Obstructive; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin; D012906:Smoke
chemical_list: D008070:Lipopolysaccharides; D055271:Mucin 5AC; D016328:NF-kappa B; D012906:Smoke; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin