The Influence Of Propofol On The GABA_AR And NMDAR1 Expression Of Hippocampus, Cortex And Thalamus Of The Rats Suffering From Inflammatory Pain

Background and Objectives:Propofol is the most commonly used intravenous anesthetics at present. It is widely used in the induction and maintenance of anesthesia, ICU sedation and the treatment of status epilepticus. Its chemical structure is different to any intravenous anesthetics, and its mechanism of anesthetic action is still in the stage of exploration. Previously the scholars believed that propofol was a hypnotic agent and it did not have analgesic effect, but according to the study of animal and clinical experiments in recent years, some scholars have confirmed that propofol has some analgesic effect in addition to sedative and hypnotic effect, but the mechanism of its analgesic effect varies due to the difference of research methods.At present, the scholars believe that the y-aminobutyric acid receptors (GABAR) and N-methyl-D-aspartate receptors(NMDAR) are the more sensitive molecular targets of propofol in relevant concentration. And A subtype (GABAAR) in the three subtypes of GABAR has the closest relations with anesthetic drugs, and both experiments in vitro and in vivo show that GABAAR and NMDAR functions have obvious influence on the anesthetic action of propofol. In addition, some scholars have proved that propofol can exert its anesthetic action by strengthening GABAAR function and the antagonism of NMDAR.N-methyl-D-aspartate receptor is a kind of ionotropic glutamate receptor. NMDAR activity has close relations with the phosphorylation sites on R1 subunit(NMDAR1), so the change of NMDAR can be reflected by studying R1 subunit in this experiment.This experiment probes the analgesic effect of propofol and its formation mechanism by studying the behavior and morphological changes of the rats suffering from formalin inflammatory pain after intraperitoneal injection of propofol.Method:32 female SD rats(weight 180-220g) were randomly divided into four groups (8 rats/group):control group, caused pain group, propofol 75mg/kg group (group P75), and propofol 100mg/kg group (group P100). Control group is blank control; and the other three groups were caused pain by injecting 0.15ml of 5% formalin in the left back palms. For propofol groups,5min before causing pain propofol 75mg/kg (group P75) and 100mg/kg (group P100) were respectively intraperitoneal injectioned. retraction counting were carried out every 5min between 5min to 60min after pain causing is started(sustaining 1 min).60min after pain causing, the average integrated optical density (IOD) were respectively observed in the value of the positive area of GABAAR and NMDAR1 protein of hippocampus, cortex and thalamus of the rats by the method of immunohistochemistry.Results:Retraction counting:compared with control group, caused pain group increase obviously (p<0.05), group P75 and group P100 increase respectively 25min and 30min later (p<0.05); compared with caused pain group, group P75 and group P100 decreased (p<0.05); and compared with group P75. group P100 decreased obviously in 25min-50min (p<0.05).The GABAAR protein expression in the three cerebral areas, i.e. cortex, hippocampus and thalamus, are as follows:compared with control group, the IOD value of pain causing group, group P75 and Group P100 increased (p<0.05); compared with caused pain group, the IOD value of group P75 and group P100 increased (p<0.05); and compared with group P75, the IOD value of group P100 increasesd (p<0.05).NMDAR1 protein expression in the three cerebral areas, i.e. cortex, hippocampus and thalamus, are as follows:compared with control group, the IOD value of pain causing group, group P75 and Group P100 increased (p<0.05); compared with caused pain group, the IOD value of group P75 and group P100 decreased (p<0.05); and compared with group P75, the IOD value of group P100 decreased(p<0.05).Conclusions:(1) Intraperitoneal injection of propofol strengthens the GABAAR expression and restrains the NMDAR1 expression of inflammatory pain of rats.(2) Sleep dosage of propofol has some analgesic effects which have relations with the GABAAR and NMDAR1 of hippocampus, cortex and thalamus.