Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway.

BACKGROUND: Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism. METHODS: SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria. RESULTS: Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ±â€Š30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ±â€Š46.8 vs. 421.7 ±â€Š48.3 pg/ml; amylase: 2102.3 ±â€Š165.3 vs. 3186.4 ±â€Š245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ±â€Š50.3 vs. 332.4 ±â€Š25.1 Hz; discharge amplitude: 33.4 ±â€Š5.3 vs. 20.5 ±â€Š2.9 µV). CONCLUSIONS: Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.

EFNB2 facilitates cell proliferation, migration, and invasion in pancreatic ductal adenocarcinoma via the p53/p21 pathway and EMT.

Ephrin-2 (EFNB2) is expressed at abnormally high levels in some neoplasms, such as squamous cell carcinoma of the head and neck and colorectal cancer. Its overexpression is associated with the malignant progression of tumors. However, the expression of EFNB2 in pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly studied. EFNB2 expression was evaluated by quantitative real-time PCR, immunohistochemistry, and western blotting. Furthermore, the association between its expression levels and the clinicopathological features of PDAC patients was explored. To determine the underlying mechanisms of EFNB2, we transfected PDAC cells with small interfering RNA and performed in vitro and in vivo experiments. EFNB2 expression levels were significantly increased in cancer tissues and were associated with PDAC clinical stage and Ki67 expression. The down-regulation of EFNB2 inhibited cell proliferation by up-regulating p53/p21-mediated G0/G1 phase blockade. Knockdown of EFNB2 decreased the migration and invasion of PDAC cells by blocking epithelial-mesenchymal transition. These results suggested that EFNB2 may participate in the development of PDAC by promoting cell proliferation, migration, and invasion. Thus, EFNB2 is a potential target for the diagnosis and treatment of PDAC.