Abstract: Objective To investigate the regulatory mechanism of atorvastatin on pulmonary vascular remodeling and expression of histone deacetylation enzyme-2 (HDAC2) in chronic obstructive pulmonary disease (COPD) rats. Methods Eighteen female SD rats were randomly divided into control group, COPD group and atorvastatin calcium group, with 6 rats in each group. The COPD model was established by passive smoking and intratracheal injection of lipopolysaccharide. From the second day, atorvastatin group was intragastrically administered with atorvastatin 10 mg/(kg·d) half an hour prior to smoking, control group and COPD group were given equal amount of normal saline at the same time. The experiment lasted six weeks. The general condition of the rats was observed during the experiment, and the body weight was weighed every two weeks. After six weeks, Hematoxylin-eosinstaining and Victoria Blue + Van Gibson VG were used to observe lung tissue pathological changes, and the degree of pulmonary vascular remodeling was evaluated. HDAC2 was determined with ELISA. The protein expression of HDAC2 was measured by Western blot assay and HDAC2 mRNA was detected by qPCR. Results At the 2nd, 4th and 6th week, compared with the control group, the body weights were decreased in COPD group (P＜0.05). Compared with COPD group, the weights of rats were increased in the atorvastain group (P＜0.05). Compared with control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in COPD group, and the vascular wall area/total vascular area (WA% ), vascular wall thickness/vascular outer diameter length (WT% ), lung inflammation score increased significantly, with the serum and lung tissue expressions of HDAC2 decreased. The level of VEGF in the lung tissue increased (P＜0.05). Compared with COPD group, the lung tissue showed less inflammatory cells in the atorvastatin group, and vascular pathological changes were significantly relieved. The WT% , WA% and lung inflammation score decreased significantly, with the expression of HDAC2 in the serum and lung tissue increased, and the level of VEGF in the lung tissue decreased (P＜0.05). Conclusion Atorvastatin calcium can reduce the degree of pulmonary vascular remodeling in COPD rats by increasing the expression and level of HDAC2.

Key words: pulmonary disease, chronic obstructive, atorvastatin calcium, rats, Sprague-Dawley, histone deacetylase 2, pulmonary vascular remodeling