In vivo effects of dexmedetomidine on immune function and tumor growth in rats with ovarian cancer through inhibiting the p38MAPK/NF-κB signaling pathway.

OBJECTIVES: During this study, we aimed to analyze the correlation between dosages of dexmedetomidine (DEX) and the p38MAPK/NF-κB signaling pathway, and their effects on immune function and tumor growth in rats with ovarian cancer (OC). METHODS: A total of 100 rats were selected for the purposes of the study. The normal group consisted of 20 rats, while the remaining 80 rats were utilized for OC model establishment purposes, and further assigned into the model, 0.2 DEX, 1 DEX and 5 DEX groups (based on respective dosages of DEX, n=20 per group). The tumor inhibition rate was calculated. Positive expressions of p38 and NF-κB in ovarian tissues were examined by means of immunohistochemical staining. Cell transformation as well as lymphocyte proliferation rates were measured using MTT. Cell cycle and apoptosis of CD4+ and CD8+ cells were determined by flow cytometry. Serum levels of IL-2 and TNF-α were detected using ELISA, while qRT-PCR and western blotting methods were used to analyze mRNA and protein expressions of p38 and NF-κB. RESULTS: Compared with the normal group, the other four groups exhibited up-regulated IL-2, TNF-α serum levels as well as up regulated expressions of p38, NF-κB65 mRNA and protein; while the respective percentages of both CD4+ and CD8+ T cells exhibited down-regulated rates. The other four groups displayed increases in tumor weight and cell apoptosis, as well as decreased levels of cell proliferation and transformation rates. The aforementioned findings of the study ultimately highlighted a greater tendency among the three DEX groups in comparison to the model group. CONCLUSION: The findings of the study suggest that a particular dosage of DEX may act to enhance the immune function of rats with OC by inhibiting the p38MAPK/NF-κB signaling pathway.

Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD.

During the present study, we explored the protective effects of autophagy on endoplasmic reticulum (ER) stress (ERS) induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague-Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke (CS)), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated 40 mg/kg CQ), and the control group (rats breathed in normal saline). The forced expiratory volume in 0.3 s/forced vital capacity (FEV0.3/FVC%), inspiratory resistance (RI), and dynamic lung compliance (Cdyn) were measured and recorded. The expressions of PKR-like ER kinase (PERK) and CCAAT/enhancer-binding protein-homologous protein (CHOP) were detected by immunohistochemistry. The cell apoptotic rates of AECs were analyzed by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labeling (TUNEL) staining. The expression levels of light chain 3 (LC3-II), p62, Beclin-1, ATG5, ATG7, Caspase-12, and Caspase-3 were detected by Western blotting. Results showed that the COPD group exhibited a lower FEV0.3/FVC% and Cdyn, and a higher RI than the control group. Compared with the control group, the integrated optical density (IOD) values of PERK and CHOP, the apoptotic rate of AECs, and expressions of LC3-II, Beclin-1, ATG5, ATG7, Caspase-3, and Caspase-12 expressions were significantly higher, whereas p62 expression was significantly lower in the COPD group. Based on the results obtained during the present study, it became clear that the inhibition of autophagy could attenuate the ERS-induced apoptosis of AECs in rats with COPD.