To Explore The Mechanism Of Wendan Decoction On Neuropsychological Abnormalities In Post - Traumatic Stress Disorder Based On GABA Energy System

Objective:To investigate the behavior changes of PTSD rats in freezingtime test and OFT after SPS for 14 days and the influence of the Chinese prescription Wen dantang. study on the immune tissue morphology changes of important cerebral cortex edge loop area, the immune positive things expression of proteins of the GABAA a 2, the expression of gene of the Postsynaptic chloride ion transporter NKCC1, KCC2 and GABAA a 2 in the cortex edge of loop and the changes of the morphology of neuronsafter 14 days of SPS and the function of Wen dantang.Methods:Through freezing time test and OFT, to observe and record the different groups rats in freezing time and OFT.Study on the immune positive things expression of GABAA a 2,postsynaptic chloride ion transporter NKCC1, KCC2 and gene expression in GABAA a 2in the hippocampus and Prefrontal cortex of the rats through HE dyeing technology, immune histochemistry, realtime PCR technology.Using transmission electron microscopy to observate and mesure the neuron morphology changesof different groups of ratsin hippocampus and prefrontal cortex.Results:After the PTSD model was establisded for 14 days, the freezing time in SPS group and Wen dantang group were very significant higher than that in control group(P<0.01). This parameter in rats of Wen dantang group were very significant significantly lower than that in SPS group (P<0.05). This parameter in rats of APZ group were very significant significantly lower than that in SPS group and Wendantang group (P<0.01). After the PTSD model was establisded for 14days, time in the center,max continuous distance on the open field of rats were significantly significant between the control group and SPS group (P<0.05). Crossing frequency has a very significant statistical differences between the control group and SPS group (P<0.01). Crossing frequency, time in the center,max continuous distance and defecations on the open field of rats were significantly significant between the Wen Dan Tang group and SPS group (P<0.05).Vertical activity has a very significant statistical differences between the APZ group and Wen dantang group (P<0.01). Max continuous distance on the open field of rats were significantly significant between the APZ group and Wen dantang group (P<0.05).Rat hippocampus HE staining results are as follows:control group of hippocampal cells morphological rules, complete, nucleus boundary clear, full, distributed evenly and closely packed, no obvious neuron degeneration necrosis; SPSgroup hippocampal cells form is irregular, the nucleus part shrink, atrophy, uneven distribution;Wen dantang group cells form improved to varying degrees.Prefrontal cortex of rats HE staining results are as follows:There is no seepage of inflammatory cellsnear the meningeal in control group of prefrontal cortex, cell morphological rules and complete;There are inflammatory cells exudationnear the multiple injuriesof meningeal inSPS group prefrontal cortex, no obvious irregular form the cell;There no obvious inflammatory factor seepsnear the meningeal inWen dantang group prefrontal cortex, some cells showed irregular shape, uneven distribution.SPS group GABAA a 2in rat hippocampus and the prefrontal cortex optical density mean has dropped significantly, and has significant difference between groups (P<0.01) After SPS 14 days, KCC2and GABAA a 2 in hippocampus in rats in SPS group dropped significantly than the control group (P<0.01).The expression of the GABAA a 2 receptor and KCC2 in the HIP of the Wen dantang group is higher than the SPS group (P<0.01). The expression of NKCC1 in the HIP of the SPS group is lower than the one of the control group (P<0.05).But, the expression of NKCC1 in the Wen dantang group in HIP is more significantlysignificant than the gene of NKCC1 in the SPS group (P<0.05).SPS group rats KCC2,NKCClin the prefrontal cortex are more declining than in control group (P<0.05). Among groups in the prefrontal cortex of rats KCC2 gene expression levels lower than control group, with statistical significance. Wen dantang group of prefrontal cortex of rats NKCC1 gene expression more lower than the SPS group, with statistical differences (P<0.05).Under transmission electron microscope, the hippocampus:after SPS, uneven distribution of SPS group of chromatin, chromatin pyknosis under nuclear membrane, a crescent shape change.Deformation of neurons in the nucleus and nuclear membrane folds, subsidence. Wen dantang group of chromatin distribution more uniform.Deformation of neurons in the nucleus and nuclear membrane folds, subsidence.Control group prefrontal cortical neurons of rats shape and nuclear membrane of neurons with clear, complete, chromatin evenly distributed.Prefrontal cortex:SPS group of chromatin distribution is extremely uneven, chromatin pyknosis under nuclear membrane, a crescent shape change.And has the obvious deformation of neurons in the nucleus and nuclear membrane in creases, subsidence of morphological changes.Wen dantang group of chromatin distribution more uniform.A tiny part of chromatin pyknosis under nuclear membrane, crescent corpuscle.Conclusions:This research have made and copied panic of PTSD model in rats successfully and the result of this experiment showed Wen dantang and APZ can significantly improve the abnormal changes of the PTSD rats’behavior in freezing time. It is preliminary evidence that the useing of Wen dantang to treathigh alertness and panic performanceof PTSD is feasible. Wen dantang can significantly improve the abnormal changes of the PTSD rats’anxiety behavior in OFT. These fuction is similar with western medicine APZ.This experiment shows thatPTSD can caused cell morphological changes in different brain regions. This change is associated with the steady-state equilibrium of cells inside and outside GABAA a 2, and Wen dantang can steady improvement effect of GABAA a 2.SPS method successfully copied PTSD rats model, can destroy the GABA system steady state of balance.Wen dantang on postsynaptic chloride ion transporter homeostatic regulation of apparent, can balance the extracellular Cl concentration inside the cell.Especially in the rat hippocampus brain regions, which may be associated with the hippocampus unique physiological characteristics.Wendantang influence neuronsmorphology changes of rats for PTSD. Which the nuclear membrane of neurons ruffle and subsidence phenomenon obviously improved in Wen dantang group.Comprehensive described above, we conclude that first,PTSDcomposed of "fright", "fear", disease involving the five zang-organs, close with bravery. The main pathogenesis of PTSD is "jing qi disorderly and chaotic ShengTan-nitrogen cementation" dynamic pathogenic process.According to the pathological characteristics of PTSD, can choose "reconcile the five internal organs, qi phlegm" Wen dantang. Second, Wen dantang can alleviate PTSD rats anxiety and panic behavior.Third, Wen dantangimprove the cell morphological abnormalities in important brain areas, increase GABAA a 2, adjust the postsynaptic steady-state to chloride ion balance state of brain-inhibition.Changes in the pathogenesis of PTSD in different regions is not the same, so different brain regions play a role in the pathogenesis of PTSD needs further research.