ABSTRACT
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.
ABSTRACT
@# Objective: To investigate the expression of Tim-3 on the surface of T cells in patients with esophageal cancer, and to explore its clinical significance. Methods: Fresh tumor tissues, paracancerous tissues, and peripheral blood were collected from 25 patients with esophageal cancer at the first affiliated Hospital of Zhengzhou University from September 2016 to April 2018. Peripheral blood from 10 healthy subjects was also collected during the same time period. The expressions of Tim-3, early apoptotic molecules and intrinsic factors in tumor tissues and peripheral blood PBMCs of 25 esophageal cancer patients were determined by flow cytometry. Also, the correlation between Tim-3+ T cell proportion and pathological parameters was investigated. The expression of Tim-3 in tumor tissues and paracancerous tissues was detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). TCGA database was used to further verify the expression of Tim-3 in tumor tissues and paracancerous tissues, as well as its relationship with prognosis. Results: Tim-3 expression on T cells was higher in tumor tissues from esophageal cancer patients (P<0.01). Tim-3+ T cell function was in an exhausted status(P<0.05 or P<0.01), and the expression of Tim-3 on the surface of T cells in esophageal cancer microenvironment was closely related to lymph node metastasis and clinical staging (all P<0.01). Conclusion: Taken together, Tim3 expression on the surface of T cells could induce T cell dysfunction in patients with esophageal cancer, suggesting that Tim-3 may serve as a potential therapeutic target for esophageal cancer.