| ObjectivePropofol is one of the most commonly used intravenous anesthetics in clinical anesthesia,mainly acting on GABAA receptor in the central nervous system to anaesthetize.However,its targedted areas in the brain are still not clear.The thalamic reticular nucleus is a thin layer of nerve cells,which cover the anterior lateral part of the thalamus,to filter a variety of sensory information entering thalamic nuclei,and to to provide a inhibitory signal for thalamic nuclei.The thalamic reticular nucleus is composed of GABAergic neurons,and has a rich expression of GABAA receptor.Recent studies suggest that the thalamic reticular nucleus is composed of functional isolated sub networks defined by anatomical connections,and there are different functional division.The anterior thalamic reticular nucleus(ATRN)and the visual thalamic reticular nucleus(VTRN)are inhibitory to proj ect to the anterior thalamic nucleus(ATN)and visual thalamic nuclei(VTN),respretively.When ATRN reduced excitability,inhibition of anterior thalamus was reduced and induced into the slow wave sleep.In contrast,when VTRN enhanced excitability,inhibition of anterior thalamus was enhanced and induced the alert state.ATRN and VTRN have an opposite function,which is evident that thalamic reticular nucleus play a vital role in sleep-arousal mechanisms.More and more evidence suggests that sleep-wake mechanism and is closely related to general anesthesia.The thalamic reticular nucleus may be one of the potential targets of propofol,therefore the aim of the paper is to explore the role of the reticular nucleus of the thalamus in the mechanism of propofol anesthesia and the possible mechanisms.MethodsAdult male SD rats were used as the experimental object,body weight 250g-300g.The following techniques including stereotaxic technique,positioning nucleus trace administration,nucleus given position tube,behavioral test,nissl staining,western-Blot,immunofluorescence were used in this research.To explore the role of the thalamic reticular nucleus in the mechanism of propofol anesthesia and the possible mechanisms,the following researches were undertaken:1)ATRN and VTRN were damaged by ibotenic acid to observe the anesthesia sensitivity and recovery time after propofol and dexmedetomidine(a2-adrenoceptor agonist)administrated.Nissl Staining method was uesd to determine the validity of the damage2)Western-Blot method was uesd to detect GABA receptor subunit β3 expression in the thalamic reticular nucleus,immunofluorescence techniques was used to detect differential expression of GAB AAreceptor β3 subunits in ATRN and VTRN.3)On the stereotaxic instrument,catheterization was done in ATRN to observe propofol sedation effects after microinjection of propofol or the propofol sensitivity after microinjection of bicuculline.Results1)Seven days after ATRN was partially damaged,the sensitivity of propofol was significantly improve;while anesthesia sensitivity of dexmedetomidine did not change significantly.In contrast,after ATRN was partially damaged,the sensitivity of propofol and dexmedetomidine did not change.However,after both ATRN and VTRN were partially damaged,the sensitivity of propofol and dexmedetomidine did not change.2)Western-Blot showed the presence of GABAA receptor β3 subunit in thalamic reticular nucleus.Immunofluorescence suggested that GABAAR-β3 is higher expressed in ATRN than in VTRN.3)Microinjection of propofol in ATRN could induce the sedation,while anethesia sensitivity was significantly reduce after microinjection of bicuculline in ATRN.ConclusionThis study preliminarily demonstrated that propofol at least partly play an important role in the anesthesia mechanism through acting on the GABAergic neurons in the anterior thalamic reticular nucleus.This process may be realized by acting on GABAA receptor in the anterior thalamic reticular nucleus,then inhibit GABAergic neuronal excitability,thereby mediating disinhibition of the anterior thalamic nuclei,and finally induce the anesthesia state. |
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