Conclusions
Atorvastatin regulates the symptoms of PAH in rats through activating the PI3K/AKT signaling pathway.
Methods
The model of PAH was successfully established in rats via hypoxia feeding. All rats were divided into three groups, including Control group (n=15), PAH model group (Model group, n=15) and atorvastatin treatment group (Ator group, n=15). Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) were detected via enzyme-linked immunosorbent assay (ELISA). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined as well. Meanwhile, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining. Furthermore, the apoptosis level of lung tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In addition, the expression levels of PI3K/AKT signaling pathway and apoptotic genes in lung tissues were detected via quantitative Polymerase Chain Reaction (qPCR).
Objective
The aim of this study was to investigate the effect of atorvastatin on pulmonary arterial hypertension (PAH) in rats and to observe its specific regulatory mechanism through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. Materials and
Results
In Model group, the levels of TNF-α and IL-6 increased significantly, while the level of NO decreased. Both RVSP and RVHI in Model group were significantly higher than those of Control group and Ator group (p<0.05). The results of HE staining revealed that Model group showed significantly severe lung tissue injury (p<0.05). According to the results of TUNEL staining, the number of apoptotic cells in lung tissues in Model group was significantly smaller than that of Ator group (p<0.05). Meanwhile, the expression level of cysteinyl aspartate-specific proteinase-3 (Caspase-3) in Model group was markedly lower than that of Ator group (p<0.05). However, the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was markedly higher than that of Ator group (p<0.05). In Ator group, the expression levels of PI3K and AKT in lung tissues were remarkably higher than those of Model group (p<0.05). All the above results indicated that atorvastatin could effectively up-regulate the expressions of PI3K and AKT (p<0.05). Conclusions: Atorvastatin regulates the symptoms of PAH in rats through activating the PI3K/AKT signaling pathway.