ABSTRACT
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: 174.2â±â30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3â±â46.8 vs. 421.7â±â48.3 pg/ml; amylase: 2102.3â±â165.3 vs. 3186.4â±â245.2 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: 456.8â±â50.3 vs. 332.4â±â25.1 Hz; discharge amplitude: 33.4â±â5.3 vs. 20.5â±â2.9 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.
Subject(s)
Dexmedetomidine , Pancreatitis , Acute Disease , Animals , Dexmedetomidine/therapeutic use , Inflammation/drug therapy , Neuroimmunomodulation , Pancreatitis/drug therapy , Rats , Tumor Necrosis Factor-alphaABSTRACT
To explicate the structure and dynamics of dominant tree populations of the natural se-condary forest in Mulanweichang, the canopy stratum composition, diameter class structure, static life table, survival curve, mortality curve, survival function and the time series prediction were studied. The results showed that there were 9 populations in canopy stratum, with Acer mono, Quercus mongolica, Tilia mandshurica and Betula platyphylla as the dominant populations. The survival curve of A. mono and T. mandshurica populations approximately belonged to Deevey-2 type, while that of Q. mongolica population and B. platyphylla population belonged to Deevey-3 type and Deevey-2 type, respectively. With the increase of diameter class, the mortality rate curves and the vanishing rate curves of all tree populations changed similarly. The maximum mortality rate and va-nishing rate of A. mono, Q. mongolica and T. mandshurica populations appeared in 4,1and1diameter class, respectively. B. platyphylla changed little over all diameter classes. The 4 survival functions showed that A. mono, Q. mongolica and T. mandshurica populations declined at early stage, but became relatively stable at intermediate and late stages. The B. platyphylla population had no obvious change. The time series prediction showed that the number of small-sized (1-2) individuals of B. platyphylla decreased gradually and tended to decline, while the populations of A. mono, Q. mongolica and T. mandshurica were fairly stable. We suspected that A. mono, Q. mongo-lica and T. mandshurica would finally dominate within this natural secondary forest.
