Determination Of Xylazole On Rat Cerebral Neuron Anesthesia Effect In Vitro

In this experiment, neurons cultured in vitro was used as reseach model, which simulated cerebral cortex neurons environment in the process of anesthesia. Anesthesia effect mechanism of xylazole on central nervous system was explored through the detection of neurotransmitter and related parameters of signal transduction pathways. It had provided theoretical and data support for further analyze the mechanism of action of xylazole, better guide clinical anesthesia drugs.The experimental results showed that the rat original generation nerve cells technology is mature and perfect which can be used as new experimental model of anesthesia mechanism research; LC-MS/MS method detecting the neurotransmitter is reliable, good accuracy, sensitivity and reproducibility which can be applied in the study of the mechanism of action of xylazole.Different concentrations of xylazole has obvious inhibitory effect on cultured neural cells secreting catecholamine neurotransmitter in vitro, which obviously increased the serotonin neurotransmitter content; It can effectively reduce the content of excited neurotransmitter Glu and Asp, while increase the content of inhibitory neurotransmitter GABA, Gly content rise after falling. In the experimental results of signal transduction pathways, xylazole had obvious inhibition on Na-K+-ATPase and Ca2+-Mg2+-ATPase activity and certain inhibition on the cAMP signal transduction pathways, that make a changing with rising and falling trend of cAMP content; The experimental results of NO-cGMP signal pathways reseach showed that in different concentrations of Xylazole, there was a trend of NO content, NOS activity and cGMP concentration significantly decreasing.We come to the conclusion:DA and NE might be the target object that xylazole played a anesthesia role, and the action mechanism of xylazole on serotonin neurotransmitter might be played through5-HT1A receptor and5-HT3receptors; Glu and Asp played an important role in the mechanism of anesthesia. GABA could participate in the xylazole anesthesia mechanism. The anesthesia mechanism principle of Gly on xylazole anesthetic needed further study. Na+-K+-ATPase and Ca2+-Mg2+-ATPase may be one of the targets that xylazole played a anesthesia role. The cAMP signal transduction pathways involved in the xylazole of anesthesia mechanism, the inhibition of xylazole on NO-cGMP signal pathways might be realised by inhibiting alpha2-adrenergic receptor which mediated pathway activation.