Study On The Molecular Mechanisms Of General Anaesthesia Mediated By Xylazole And Its Compound Agent

【Objectives】The principle focus of this study was to clarify the anesthetic mechanisms ofalpha-2 adrenoceptor agonists and its compound anesthetic agent-QFM combination.【Materials and Methods】The hemodynamic effects of QFM combination and its molecularmechanisms were investigated systemicaly in this study, in which the hemodynamic changeswere recorded by using Datex CardiocapTMⅡCH-RS circulation monitor in dogs anesthetizedwith QFM combination, and its correlating factors of blood cytokine, neuropeptides,neurotransmitters in blood samples in phase were measured by radioimmunoassay andcolorimetry methods. The transmembrane cells signaling transduction mechanisms of generalanesthesia mediated by xylazole and QFM combination in rats'central nervous system (CNS)were investigated systemically by using colorimetry methods to determine the ATPase activitiesof synaptosomal membranes in cerebral cortex, hippocampus, cerebellum and brain stem, whichwere isolated by differential centrifugation. In this study, the intracellular signaling transductionmechanisms of general anesthesia mediated by xylazole and QFM combination in rats'centralnervous system (CNS) were also investigated systemically by using colorimetry andradioimmunoassay methods to determine the effects of xylazole and QFM combination onNO-NOS-cGMP and AC-cAMP-PDE signaling pathways.【Results】The results of this experiment are as follows:1 The molecular mechanisms of hemodynamic changes in dogsanesthetized with QFM combination (1)Significant hemodynamic changes were found in dogs anesthetized with QFMcombination injection intravenously. The results showed that systolic blood pressure (SBP),diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) duringanesthetic period significantly decreased compared with the baseline values of preanesthesia,which persisted in all the monitoring period. Although QFM combination had significant effectson hemodynamic parameters in dogs,the changes of these parameters were all in physiologicalranges. (2)QFM combination decreased the values of hemodynamic parameters, while in phase,decreased the concentrations of plasma endothelin(ET)and theomboxane A2(TXA2), andimproved the concentrations of serum nitric oxide(NO)and plasma 6-keto- prostacyclin F1α III东北农业大大学农学博士学位论文(6-Keto-PGF1α)and the ratio of NO/ET and 6-Keto-PGF1α/TXB2 in dogs. The changes ofhemodynamic parameters SBP, DBP, MAP and HR fitted well with that of endothelium-derivedvasoactive factors, and correlated with each other significantly, whichsuggested that the level ofserum NO, plasma level of PGI2, ET and TXA2 might modulate the hemodynamic changesmediated by QFM combination. (3)QFM combination decreased the values of hemodynamic parameters, while in phase,decreased the plasma rennin activity and the concentrations of plasma angiotensin AⅡin dogs.The changes of hemodynamic parameters SBP, DBP, MAP and HR fitted well with that ofplasma rennin activity and concentrations of plasma angiotensin AⅡ, and correlated with eachother significantly, which suggested that the renin- angiotonin –aldosterone-system mightmodulate the hemodynamic changes mediated by QFM combination. (4)QFM combination decreased the values of hemodynamic parameters, while in phase,decreased the plasma concentrations of neuropeptide Y in dogs. The changes of hemodynamicparameters SBP, DBP, MAP and HR fitted well with that of plasma concentrations ofneuropeptide Y, and correlated with each other significantly, which indicated that the plasmaneuropeptide Ymight play an important role in modulating the hemodynamic changes mediatedby QFM combination. (5)QFM combination decreased the values of hemodynamic parameters, while in phase,improved the plasma concentrations of neurotensin in dogs. The changes of hemodynamicparameters SBP, DBP, MAP and HR fitted well with that o...