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| Effect of early intervention of Simvastatin on chronic obstructive pulmonary disease rats model |
| YANG Kai1 GUO Lu2▲ LIU Yuejian2 HU Rong1 DUAN Wenjuan3 |
1.Department of Respiratory, the First Affiliated Hospital of Chengdu Medical College, Sichuan Province, Chengdu 610500, China;
2.Department of Respiratory, Sichuan Provincial People′s Hospital, Sichuan Province, Chengdu 610072, China;
3.Department of Pediatrics, the First Affiliated Hospital of Chengdu Medical College, Sichuan Province, Chengdu 610500, China |
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Abstract Objective To explore the effects of early stage administration of Simvastatin on chronic obstructive pulmonary disease (COPD) rat model and its mechanism. Methods 42 SPF Wistar rats were randomly divided into three groups (n=14): blank group, model group and Simvastatin group. COPD rat models were replicated with the method of inhaling cigarette smoke and intratracheal instillation of LPS. Simvastatin group rats were gave lavage treatment with Simvastatin (5 mg/kg) after 2 weeks when COPD model was established. Usual manifestations and body weights of rats from the three groups were monitored. The levels of IL-6 and TNF-α in serum and BALF were measured by double antibody sandwich enzyme-linked immuno sorbent assay (ELISA). Leukocyte in BALF was counted by haemocytometer. The expression of MMP-9 in the lung tissues was measured by immunohistochemically. Pathological examination of lung tissues from every group was analyzed by image analysis system. Results Body weights of rats from the model group and Simvastatin group were significantly reduced compared with those of the blank group (P ＜ 0.01). Levels of IL-6 and TNF-α in serum and BLAF were higher in the model group and Simvastatin group than the blank group (P ＜ 0.05). Compared with model group, the levels in Simvastatin group were decreased (P ＜ 0.05). The expression of MMP-9 in lung tissues, model group was increased than the blank group (P ＜ 0.05), Simvastatin group was lower than the model group (P ＜ 0.05). The pathologic characteristics of COPD was observed in the lung tissues from Simvastatin group and model group. Copmared with the model group, lung tissue injury, remodeling and inflammatory infiltration in Simvastation group was attenuated. Conclusion Cigarettes inhalation combined with respiratory infections can aggravate pulmonary and systemic inflammation, and up-regulate the expression of proteases, all of which are involved in the genesis and development of COPD. Simvastatin therapy as an early intervention can alleviate the lung tissue injury and remodeling to a certain degree, attenuate pulmonary and systemic inflammation and alleviate the over-activation of proteasesystem.
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