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Abstract Objective To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. Methods Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). Results Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p< 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p< 0.05). Conclusion The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.
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The research observed the effect of Yiqigubiao Pill regulating inflammatory reaction mRNA expression in JAK/STAT pathway in COPD rats model and explored protective effect of Yiqigubiao pills in the treatment or auxiliary possible mechanism in COPD. 60 SFP Wistar rats were divided randomly into control group (CN), COPD model group (M) and Yiqigubiao Pill group (Yqgb). The rats in group M and group YQGB were establish by using the method of LPS and smoking as COPD, rats in group M and group CN were given normal saline intragastric administration, and rats in the YQGB group were given water solution intragastric administration at the corresponding dose, twice a day. After using drugs for 12 weeks, we used ELISA method to detect changes inIL-17a, IL-23, IFN-γ and RORγt expression in peripheral blood, RT-PCR method to detect changes in the expression of JAK1, JAK3, STAT1 and STAT3 mRNA in lung tissues. Compared with the group CN, the infiltration of inflammatory cells stained by HE in the experimental group was reduced, and the diameter of the bronchial lumen was broadened (P ＜ 0.01). Both of ELISA and RT-PCR results showed that, compared with group CN, the levels of IL-17a, IL-23 and RORγt, the levels of JAK1, JAK3, STAT1, and STAT3 mRNA were increased in group M. Compared with group M, the mRNA levels of above indicators in group Yqgb were decreased, and the difference was statistically significant (P ＜ 0.01). Correlation analysis revealed that JAK1, JAK3, STAT1 and STAT3 were associated with IL-17a, IL-23, and RORγt had statistical significance (P ＜ 0.05). Therefore, Yiqgubiao Pill can inhibit the inflammatory response in COPD rats model, and its mechanism may be associated with inhibition of JAK/STAT pathway.