Sheng Wang1, Lingling Xiong2, Xue Deng2, Wei Ren2, Chundong Zhu2, Chunying Li2, Qun Zhou2. 1. Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China; Email: ahzyws@163.com. 2. Department of Geriatric Respiratory Medicine, First Affiliated Hospital, Anhui University of TCM, Hefei 230031, China.
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.
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.