| Post-traumatic Stress Disorder(PTSD) is a kind of delayed or persistent anxiety stressed disorder which is caused by experiencing unusual events or threatening situation.The neurobiological pathogenesis of PTSD are anfractuous, Recent studies suggested that NO related pathways closely related to inflammatory factors, the formation of fear traumatic memories and down-regulation of neurogenesis, which may play an important role in the occurrence mechanism of PTSD. Propofol as the most prevalent intravenous anesthetic in clinical practice, has broad and complex action mechanisms, however there are a lot of the non-anesthesia effects,such as anti-anxiety, neuroprotection, inhibiting lipid peroxidation and anti-inflammatory in regulating immune response. The previous research proves that propofol has anti-PTSD effects on mouse inescapable electric foot shock model and mice time-dependent sensitization model.In this study, we investigate the anti-PTSD effect of propofol in the classic fear conditioning rats and the further step to study the potential relationship between the anti-inflammatory, neuroprotection of propofol and inflammation-i NOS-NO pathway,NO-neuroplasticity in the PTSD.This study intends to use fear conditioning model in rats, establishing conditioned fear stress in rats by electric shock with tone as a prompt, to evaluate the anti-PTSD effect of propofol by testing the rats freezing time.Basing on the model, the NO contents, neurons nitric oxide synthase(n NOS) and inducible nitric oxide synthase(i NOS) protein level on amygdale and hippocampus of rats in each group were detected by Griess method and Western blotting method, inflammatory factor levels weredetected by inflammatory factor(Interleukin-1?, Interleukin-6 and tumor necrosis factor-?) Elisa kits, the changes of hippocampal neuronal plasticity was analyzed by rapid Golgi Stain kit; In vitro, the effect of propofol on the level of NOS were analyzed by Western blotting method in the C6 glioma cell, to explore the influence of propofol on the NOS and the potential connection with GABAA receptor.The research results are as the following:(1)It was showed by the behavior tests that freezing time in extinction control group and extinction training group were significantly increased compared with control group(P< 0.001), extinction training group freezing time has no significant differences compared with extinction control group, which hints that fear conditioning model is made successfully. Freezing times in sertraline group were significantly decreased( P<0.01)compared with extinction training group at at the 1,4 and 7th day after conditioned fear extinction training in the rats; While freezing times of propofol( 0.3,1.0 mg/kg) groups were significantly reduced( P<0.01)at the 4 and 7th day after conditioned fear extinction training in the rats.(2)To detect the NO contents by Griess method showed that the content of NO on the amygdale and hippocampus of rats in extinction control group and extinction training group were significantly increased compared with control group(P<0.001),extinction training group the content of NO has no significant differences compared with extinction control group; the level of NO on the amygdale and hippocampus of rats in sertraline and propofol( 0.3, 1.0 mg/kg) groups were significantly decreased( P<0.01)compared with extinction training group.(3)It was showed by Western blotting that the levels of i NOS/n NOS on the amygdale and hippocampus of rats in extinction control group and extinction training group were significantly increased compared with control group(P < 0.001), extinction training group NOS levels has no significant differences compared with extinction control group; sertraline and propofol( 0.3, 1.0 mg/kg) groups were significantly reduced the thelevels of i NOS/n NOS(P<0.01) compared with extinction training group.(4)It was showed by Elisa kits that the contents of IL-1??IL-6 and TNF-?on the amygdale and hippocampus of rats in extinction control group and extinction training group were significantly increased compared with control group(P < 0.001), extinction training group the contents of inflammatory factors has no significant differences compared with extinction control group; sertraline and propofol( 0.3,1.0 mg/kg) groups were significantly reduced the IL-1? ? IL-6 and TNF-? contents( P <0.01)compared with extinction training group.(5)It was showed by Elisa kits that rapid Golgi Stain that neuronal dendritic length and branchs,dendritic spines density on the hippocampus of rats in extinction control group and extinction training group were significantly increased compared with control group(P<0.001), extinction training group neuronal dendritic has no significant changes compared with extinction control group;sertraline and propofol( 0.3,1.0 mg/kg) groups were obviously increased hippocampal neuronal dendritic length and branchs, dendritic spines density( P<0.001)compared with extinction training group.(6)In vitro, it was showed that propofol could inhibit obviously the expression of i NOS and n NOS(P < 0.01);After antagonism with bicuculline(50umol/L),it could reverse the reduced level of i NOS and n NOS by propofol(P<0.05).These results suggested that propofol could ruduce conditioned fear memory, has preferable anti-PTSD effects on the model of fear condition in rats, the underlying mechanism may involves inflammation-i NOS-NO pathway and the change of NO-neuroplasticity; the inhibition of over-released NO may related to GABAA receptor. |
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