Study On Effect Of Histamine Neurotransmitters In The Mechanism Of Propofol-induced Loss And Recovery Of Consciousness

Background and objective: Since the first general anesthesia operation was completed in Massachusetts General Hospital in 1846,general anesthetics have been developing for more than 170 years,but the mechanism of reversible consciousness loss and recovery has not yet been elucidated.In recent years,many studies have found that the tuberomammillary nucleus(TMN)play an important role in regulating sleep and maintaining wakefulness.The histamine released from TMN is an important neurotransmitter in the regulation of wakefulness.However,how propofol affects the level of histamine in central nervous system and the behavioral changes associated with histamine receptor antagonist are rarely reported.In this study,we used the methods of microdialysis and reverse dialysis to study the role of histamine neurotransmitters in propofol general anesthesia.Methods1.12 SPF healthy male adult SD rats were randomly divided into propofol experimental group(n=6)and TMN control group(n=6).After the TMN microdialysis models were established,the histamine levels were measured.The experimental group was balanced for two hours before propofol anesthesia.A single inducing dose of propofol(11 mg/kg)was injected through the tail vein.After the loss of righting reflex(LORR),the rats were infused with propofol(40 mg/kg)for 1hour.The dialysates were collected for another 1.5 hour after recovering of righting reflex.Each control group was given the same volume of saline instead of propofol.Histamine levels in posterior hypothalamus areas during propofol general anesthesia were detected by high performance liquid chromatography.2.The behavioral experiment was divided into 2 groups,the thioperamide group(n=8)and the artificial cerebrospinal fluid(ACSF)control group(n=8).A tail catheter was placed.The ACSF containing H3 R antagonist and normal ACSF were perfused inthe posterior hypothalamus area through the dialysis probe.After balance of 1 hour,the inducing dose of propofol(11 mg/kg)was given through the tail vein.The time of RORR was measured after LORR.Results1.Compared with the saline group,the histamine transmitters level in posterior hypothalamus area was decreased during the induction and maintenance of propofol(P < 0.05).2.Compared with the ACSF group,the RORR time of propofol general anesthesia was shortened by H3 R antagonist thioperamide.(P<0.05).Conclusion1.The synthesis or release of histamine transmitters can be inhibited during the induction and maintenance of propofol general anesthesia,and the level of histamine transmitters in the posterior hypothalamus can be reduced by propofol general anesthesia.Histamine neurotransmitter participates in the process of consciousness disappearance caused by propofol general anesthesia.2.H3 R antagonist thioperamide can accelerate the recovery process of propofol general anesthesia.