發(fā)布時(shí)間：2018-05-06 16:05

  本文選題：抑郁癥 + PFC-NAc-VTA神經(jīng)環(huán)路�。� 參考：《湖北中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：目的抑郁癥逐漸成為現(xiàn)代社會(huì)的常見(jiàn)及高發(fā)疾病,給社會(huì)和患者的生活都帶來(lái)了巨大的壓力,但抑郁癥發(fā)病機(jī)制復(fù)雜,明確抑郁癥的發(fā)病機(jī)制,對(duì)于抑郁癥的診治至關(guān)重要。本研究以中醫(yī)“肝郁”與抑郁癥的相似性為切入點(diǎn),基于抑郁模型PFC-NAc-VTA神經(jīng)環(huán)路的病理生理變化,旨在闡釋中醫(yī)“肝郁”發(fā)生的中樞機(jī)制,并通過(guò)觀(guān)察疏肝和胃湯對(duì)抑郁模型PFC-NAc-VTA神經(jīng)環(huán)路的影響作用研究其抗抑郁機(jī)制,為深入研究中醫(yī)藥治療抑郁癥提供理論和實(shí)驗(yàn)依據(jù)。方法1.理論研究:采用文獻(xiàn)分析法,歸納古今醫(yī)家對(duì)抑郁癥相關(guān)病證的臨床辨治規(guī)律,并梳理《傷寒雜病論》中抑郁癥相關(guān)病證的辨治規(guī)律,分析中醫(yī)肝郁與抑郁癥的相關(guān)性;通過(guò)整理PFC-NAc-VTA神經(jīng)環(huán)路與抑郁癥發(fā)病的聯(lián)系,分析中醫(yī)肝郁的中樞機(jī)制與PFC-NAc-VTA神經(jīng)環(huán)路的相關(guān)性。2.實(shí)驗(yàn)研究:(1)模型制作及評(píng)價(jià):采用慢性不可預(yù)知性應(yīng)激結(jié)合孤養(yǎng)法造模4w,造模完成后給予三種不同濃度疏肝和胃湯及氟西汀干預(yù)7d,并運(yùn)用曠場(chǎng)實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn)進(jìn)行行為學(xué)評(píng)價(jià)。(2)神經(jīng)環(huán)路相關(guān)指標(biāo)的檢測(cè):采用尼氏染色法觀(guān)察抑郁模型大鼠PFC腦區(qū)切片的病理改變,并統(tǒng)計(jì)PFC區(qū)正常神經(jīng)元的數(shù)目;采用高效液相法分別檢測(cè)抑郁模型大鼠PFC、NAc及VTA三個(gè)腦區(qū)中DA、GABA、Glu含量;采用RT-PCR檢測(cè)抑郁模型大鼠NAc區(qū)PSD95m RNA、NR2B m RNA的相對(duì)表達(dá)量;采用western blot檢測(cè)抑郁模型大鼠NAc區(qū)PSD95、NR2B的相對(duì)表達(dá)量。結(jié)果1.理論研究:古代醫(yī)家認(rèn)為,抑郁癥與情志之郁證關(guān)系密切,可兼夾諸郁,又涉及臟腑功能紊亂及氣血津液的失調(diào)。現(xiàn)代臨床辨證規(guī)律研究顯示,情志失調(diào)為抑郁癥的主要病因,肝失疏泄為抑郁癥病機(jī)核心,以影響及心、脾、胃等多臟腑為抑郁癥的傳變特點(diǎn),以氣血津液陰陽(yáng)失調(diào)為抑郁癥的病理變化特點(diǎn),治法以疏肝解郁,調(diào)暢氣機(jī)為主�，F(xiàn)代醫(yī)學(xué)認(rèn)為抑郁癥的發(fā)病機(jī)制與PFC-NAc-VTA神經(jīng)環(huán)路的功能失調(diào)相關(guān),因此可以從PFC-NAc-VTA神經(jīng)環(huán)路為切入點(diǎn)探討“肝郁”的中樞機(jī)制。2.實(shí)驗(yàn)研究:實(shí)驗(yàn)一:疏肝和胃湯對(duì)抑郁模型大鼠行為學(xué)的影響(1)模型組曠場(chǎng)實(shí)驗(yàn)靜止時(shí)間延長(zhǎng),與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組靜止時(shí)間縮短,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(2)模型組曠場(chǎng)實(shí)驗(yàn)總運(yùn)動(dòng)距離縮短,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組總運(yùn)動(dòng)距離增加,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中劑量組總運(yùn)動(dòng)距離較氟西汀組長(zhǎng),差異有統(tǒng)計(jì)學(xué)意義(P0.01),高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)模型組曠場(chǎng)實(shí)驗(yàn)中央?yún)^(qū)域穿越格數(shù)減少,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中、高劑量組及氟西汀組中央?yún)^(qū)域穿越格數(shù)增多,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(4)模型組強(qiáng)迫游泳實(shí)驗(yàn)不動(dòng)時(shí)間延長(zhǎng),與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組不動(dòng)時(shí)間縮短,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。實(shí)驗(yàn)二:疏肝和胃湯對(duì)抑郁模型大鼠PFC區(qū)病理變化的影響(1)光鏡下尼氏小體呈深藍(lán)色或紫藍(lán)色,多為塊狀或細(xì)顆粒狀,分布于核周?chē)�或�?shù)突內(nèi),尼氏體靠近胞體周?chē)�處較為明顯�？瞻捉MPFC區(qū)神經(jīng)元數(shù)目較多,尼氏小體顏色較深,分布于細(xì)胞核周?chē)�。神�?jīng)元細(xì)胞形態(tài)飽滿(mǎn),結(jié)構(gòu)完整,邊緣清晰;模型組PFC區(qū)神經(jīng)元數(shù)目相對(duì)較少,尼氏小體顏色較淡,分布疏松,細(xì)胞形態(tài)不規(guī)則,結(jié)構(gòu)不完整,尼氏小體數(shù)目減少或消失,部分細(xì)胞核偏向一側(cè),細(xì)胞腫大,出現(xiàn)空泡區(qū);經(jīng)過(guò)治療藥物干預(yù)后,各治療組尼氏小體數(shù)目較模型組增多但少于空白組,較模型組尼氏小體顏色更深,結(jié)構(gòu)較完整、清晰。(2)模型組PFC區(qū)正常神經(jīng)細(xì)胞數(shù)量減少,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組PFC區(qū)正常神經(jīng)細(xì)胞數(shù)量增加,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。實(shí)驗(yàn)三:疏肝和胃湯對(duì)抑郁模型大鼠PFC-NAc-VTA神經(jīng)環(huán)路中DA、GABA、Glu含量的影響(1)PFC區(qū)中,模型組DA含量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中、高劑量組及氟西汀組DA含量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);其中,疏肝和胃湯高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。NAc區(qū)中,模型組DA含量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組DA含量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);其中,疏肝和胃湯中劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。VTA區(qū)中,模型組DA含量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯低、中劑量組及氟西汀組DA含量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);其中,疏肝和胃湯低、中劑量組DA含量較氟西汀組低,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。(2)PFC區(qū)中,模型組Glu含量升高,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組Glu含量降低,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中劑量組Glu含量較氟西汀組低,差異有統(tǒng)計(jì)學(xué)意義(P0.05),低、高劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。NAc區(qū)中,模型組Glu含量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中劑量組及氟西汀組Glu含量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。VTA區(qū)中,模型組Glu含量升高,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組Glu含量降低,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);其中,疏肝和胃湯各劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)PFC區(qū)中,模型組GABA含量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中劑量組及氟西汀組GABA含量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。NAc區(qū)中,模型組GABA含量升高,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中、高劑量組GABA含量降低,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組與氟西汀組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。VTA區(qū)中,模型組GABA含量升高,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯中劑量組及氟西汀組GABA含量降低,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。實(shí)驗(yàn)四:疏肝和胃湯對(duì)抑郁模型大鼠NAc區(qū)PSD95 m RNA和NR2B m RNA表達(dá)的影響(1)模型組NAc區(qū)PSD95 m RNA的相對(duì)表達(dá)量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組NAc區(qū)PSD95 m RNA的相對(duì)表達(dá)量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組PSD95 m RNA的相對(duì)表達(dá)量高于氟西汀組,差異有統(tǒng)計(jì)學(xué)意義(P0.01);低劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(2)模型組NAc區(qū)NR2B m RNA的相對(duì)表達(dá)量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05);疏肝和胃湯各劑量組及氟西汀組NAc區(qū)NR2B m RNA的相對(duì)表達(dá)量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯各劑量組NAc區(qū)NR2B m RNA的相對(duì)表達(dá)量高于氟西汀組,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。實(shí)驗(yàn)五:疏肝和胃湯對(duì)抑郁模型大鼠NAc區(qū)PSD95和NR2B表達(dá)的影響(1)模型組NAc區(qū)PSD95相對(duì)表達(dá)量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組PSD95相對(duì)表達(dá)量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯中、高劑量組PSD95相對(duì)表達(dá)量高于氟西汀組,差異有統(tǒng)計(jì)學(xué)意義(P0.01),低劑量組與氟西汀組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(2)模型組NAc區(qū)NR2B相對(duì)表達(dá)量降低,與空白組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);疏肝和胃湯各劑量組及氟西汀組NR2B相對(duì)表達(dá)量升高,與模型組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01);其中,疏肝和胃湯低、中劑量組NR2B相對(duì)表達(dá)量高于氟西汀組,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。結(jié)論1.古代醫(yī)家所論之“郁”涉及范圍較廣,包括五運(yùn)六氣之郁、臟腑之郁及情志之郁等,至明清以后專(zhuān)論郁證,才與現(xiàn)代抑郁之“郁”聯(lián)系緊密。2.近十年來(lái)抑郁癥的中醫(yī)病因及證候分布規(guī)律研究顯示,情志失調(diào)為抑郁癥的主要病因,肝失疏泄為其病機(jī)核心,以影響及心、脾、胃等多臟腑為其傳變特點(diǎn),以氣血津液陰陽(yáng)失調(diào)為其病理變化特點(diǎn),治法以疏肝解郁,調(diào)暢氣機(jī)為主。3.慢性應(yīng)激引起的PFC區(qū)神經(jīng)元病理改變,PFC-NAc-VTA神經(jīng)環(huán)路DA含量的降低、Glu含量的升高、GABA含量的相應(yīng)改變,以及NAc區(qū)突觸相關(guān)蛋白PSD95、NR2B及其m RNA表達(dá)的下降,可能是抑郁癥的發(fā)病機(jī)制。4.疏肝和胃湯能夠改善抑郁模型大鼠的抑郁狀態(tài),并且能減輕抑郁模型大鼠PFC區(qū)神經(jīng)元的受損程度,調(diào)節(jié)PFC-NAc-VTA神經(jīng)環(huán)路中DA、Glu、GABA含量的異常上升或下降,且能夠逆轉(zhuǎn)模型大鼠NAc區(qū)突觸相關(guān)蛋白PSD95、NR2B及其m RNA的異常下調(diào),提示疏肝和胃湯可能是通過(guò)對(duì)PFC-NAc-VTA神經(jīng)環(huán)路中上述指標(biāo)的調(diào)節(jié)發(fā)揮抗抑郁作用的。5.中醫(yī)“肝郁”發(fā)生的中樞機(jī)制可能與PFC區(qū)神經(jīng)元病理變化,PFC-NAc-VTA神經(jīng)環(huán)路中DA、Glu、GABA的異常表達(dá)以及NAc區(qū)突觸相關(guān)蛋白PSD95、NR2B及其m RNA的異常下調(diào)有關(guān)。6.研究結(jié)果提示,疏肝和胃湯發(fā)揮抗抑郁作用的潛在機(jī)制之一,可能是通過(guò)調(diào)節(jié)PFC-NAc-VTA神經(jīng)環(huán)路中的多個(gè)靶點(diǎn)實(shí)現(xiàn)的。
[Abstract]:Objective depression has gradually become a common and high incidence disease in modern society, which brings great pressure to the life of society and patients. However, the pathogenesis of depression is complicated. The pathogenesis of depression is very important for the diagnosis and treatment of depression. This study is based on the similarity of "liver depression" with depression, based on depression and depression. The pathophysiological changes of the model PFC-NAc-VTA nerve loop are designed to explain the central mechanism of "liver depression" in Chinese medicine, and to study the antidepressant mechanism of the depression model PFC-NAc-VTA neural loop by observing the effect of Shugan and stomach soup on the depression model, and to provide theoretical and experimental basis for the in-depth study of Chinese medicine for the treatment of depression. Method 1. theory study: Using the method of literature analysis, this paper summarizes the law of the clinical differentiation and treatment of depression related syndromes by ancient and modern doctors, and combs the law of differentiation and treatment of the syndrome of depression related to depression in the theory of typhoid and miscellaneous diseases, analyzes the correlation between the liver depression and depression of traditional Chinese medicine, and analyzes the central mechanism and PFC-N of the liver depression of traditional Chinese medicine by sorting out the connection between the PFC-NAc-VTA nerve loop and the depressive disorder. The correlation.2. experimental study of Ac-VTA neural loop: (1) model making and evaluation: using chronic unpredictable stress combined with soliton method to create a model of 4W, after the completion of the model, three different concentrations of liver and stomach soup and fluoxetine intervention were given, and the field experiment was used to evaluate the behavior of the forced swimming test. (2) the examination of the related indexes of the nerve loop. Test: the pathological changes in the PFC brain section of the depressive model rats were observed by Nissl's staining, and the number of normal neurons in the PFC region was measured. The content of DA, GABA and Glu in the three brain regions of the depressive model rats were detected by high performance liquid phase method, and the relative expression of PSD95m RNA in the NAc region of the depressive model rats was detected by RT-PCR. Western blot was used to detect the relative expression of PSD95 and NR2B in the NAc area of the depression model rats. Results 1. theoretical study: ancient doctors believed that depression was closely related to emotional depression syndrome, and it could be combined with depression and imbalance of viscera function and Qi and blood body fluid. Modern clinical syndrome differentiation study showed that emotional disorder was the main disease of depression. As the core of the depression, liver loss and catharsis are the core of the depression, and the multiple Zang Fu organs such as the heart, the spleen and the stomach are the characteristics of the depressive disorder, and the pathological changes of depression are characterized by the imbalance of Qi and blood Yin and Yin and Yin and Yang, and the treatment method is mainly to remove the stagnation of the liver and regulate the Qi, and the pathogenesis of depression is related to the dysfunction of the PFC-NAc-VTA nerve loop. The experimental study on the central mechanism of "liver depression" can be studied from the PFC-NAc-VTA neural loop as the breakthrough point. Experiment 1: the effect of Shugan Hewei decoction on the behavior of the depression model rats (1) the time of the static time of the model group was prolonged, and the difference was statistically significant (P0.01), the dosage group of Shugan Hewei decoction and the static fluoxetine group were static. There was significant difference between the model group and the model group (P0.01), and there was no significant difference between the high dose group of Shugan Hewei decoction and the fluoxetine group (P0.05). (2) the total movement distance of the model group was shorter than that in the blank group (P0.01); the total dose group of Shugan Hewei decoction and the general transport of fluoxetine group were compared with that of the blank group. The difference of dynamic distance between the model group and the model group was statistically significant (P0.01), and the total motion distance of the dose group in the liver and stomach soup was more significant than that of the fluoxetine group (P0.01). There was no significant difference between the high dose group and the fluoxetine group (P0.05). (3) the number of crossing lattices in the central area of the model group was reduced and the blank group was in the blank group. The difference was statistically significant (P0.01); in the high dose group and the fluoxetine group, the number of crossing lattices increased in the high dose group and the fluoxetine group, and there was a significant difference between the model group and the model group (P0.01). There was no significant difference between the high dose group and the fluoxetine group (P0.05). (4) the time of the forced swimming test in the model group was not significant. The difference has statistical significance (P0.01) compared with the blank group, and the time of each dose group and fluoxetine group in the Shugan Hewei decoction group and the fluoxetine group were shorter than the model group (P0.01). The difference between the high dose group and the fluoxetine group was not statistically significant (P0.05). Experiment two: the depression of liver and stomach soup to the depression model. The effect of pathological changes in PFC area of type rats (1) the Nissl body was dark blue or purple blue under light microscope, mostly massive or fine grainy, distributed around the nucleus or dendrite, Nissl body was near the cell body. The number of neurons in the blank group PFC area was more, the Nissl body color was deep and distributed around the nucleus. Full, complete structure, clear edge; the number of neurons in the model group PFC is relatively small, Nissl body color is light, loose, irregular cell morphology, incomplete structure, the number of Nissl corpuscles decreasing or disappearing, partial nucleus to one side, cell enlargement, empty bubble area; after treatment of drug after the prognosis, the number of Nissl corpuscles in the treatment group More than the model group but less than the blank group, Nissl body color was deeper and more complete and clear than the model group. (2) the number of normal nerve cells in the PFC area of the model group decreased, and the difference was statistically significant (P0.01). The number of normal nerve cells in each dose group of Shugan Hewei decoction and the PFC area of fluoxetine group was increased, and the difference was compared with the model group. There was statistical significance (P0.01); among them, there was no significant difference between the high dose group and the fluoxetine group (P0.05). Experiment three: the effect of Shugan Hewei decoction on the content of DA, GABA and Glu in the PFC-NAc-VTA nerve loop of the depression model rats (1) the DA content in the model group decreased, and the difference was statistically significant (P0.) compared with the blank group (P0.) 01): the content of DA in the high dose group and the fluoxetine group increased in the high dose group and the fluoxetine group. The difference was statistically significant (P0.05 or P0.01) in the model group (P0.05 or P0.01), and there was no significant difference between the high dose group and the fluoxetine group (P0.05) in.NAc area, and the content of the model group decreased, and the difference was statistically significant (P0.01). The DA content in each dose group of liver and stomach soup and fluoxetine group was higher than that in the model group (P0.05 or P0.01), and there was no significant difference in the dose group of the liver and stomach soup with the fluoxetine group (P0.05) in.VTA area (P0.05), the model group had a lower DA content, and the difference was statistically significant (P0.01) compared with the blank group (P0.01); the liver and stomach soup had a significant difference (P0.01). The DA content in the middle dose group and the fluoxetine group was higher than that in the model group (P0.05 or P0.01), in which the liver and stomach soup were low and the medium dose group DA content was lower than that of the fluoxetine group (P0.01). (2) in the PFC region, the Glu content in the model group increased, and the difference was statistically significant (P0.01) compared with the blank group (P0.01); and the liver soothing and the liver of the group were statistically significant (P0.01). The contents of Glu in each dose group and fluoxetine group were lower than those in the model group (P0.01), and the Glu content in the dose group of the liver and stomach soup was lower than that in the fluoxetine group (P0.05), and the difference was lower in the high dose group than in the fluoxetine group (P0.05).NAc region, and the Glu content in the model group decreased. Compared with the blank group, the difference was statistically significant (P0.01). The content of Glu in the dose group and the fluoxetine group in the Shugan Hewei decoction and the fluoxetine group had a significant difference (P0.01), and the difference between the dose group of the liver and the stomach soup was not statistically significant (P0.05).VTA region, and the Glu content in the model group was higher than that in the blank group, and compared with the blank group. The difference was statistically significant (P0.01); the content of Glu in each dose group of Shugan Hewei decoction and fluoxetine group decreased significantly (P0.05 or P0.01) compared with the model group (P0.05 or P0.01), and there was no significant difference between each dose group of Shugan Hewei decoction and fluoxetine group (P0.05). (3) in the PFC region, the content of GABA in the model group decreased and the difference was different from that of the blank group. There was statistical significance (P0.01); the content of GABA in the dose group and the fluoxetine group in the Shugan Hewei decoction group was higher than that in the model group (P0.01). There was no significant difference in the dose group between the soothing liver and the stomach soup and the fluoxetine group (P0.05) in.NAc region, and the GABA content in the model group increased, and the difference was statistically significant compared with the blank group. P0.01; in the liver and stomach soup, the content of GABA in the high dose group decreased, and the difference between the model group and the model group was statistically significant (P0.01). In the liver and stomach soup, the high dose group and the fluoxetine group were compared with the fluoxetine group, the difference was statistically significant (P0.01) in the.VTA region, the GABA content in the model group increased, and the difference was statistically significant (P0.01) compared with the blank group (P0.01); the liver and the stomach were significantly different from the blank group. The content of GABA in the medium dose group and the fluoxetine group decreased, and there was a significant difference between the model group and the model group (P0.01). There was no significant difference between the dose group in the Shugan Hewei soup and the fluoxetine group (P0.05). Experiment four: the effect of Shugan Hewei decoction on the expression of PSD95 m RNA and NR2B m RNA in the NAc region of the depressive model rats (1) NAc District PSD95 The relative expression of M RNA was lower than that in the blank group (P0.01), and the relative expression of PSD95 m RNA in each dose group of Shugan Hewei decoction and the PSD95 m RNA in fluoxetine group was higher than that in the model group (P0.01), and the relative expression of PSD95 m RNA in the high dose group was higher than that of fluoxetine in the liver and stomach soup. The difference was statistically significant (P0.01), and there was no significant difference between the low dose group and the fluoxetine group (P0.05). (2) the relative expression of NR2B m RNA in the NAc area of the model group was reduced, and the difference was statistically significant (P0.05), and the relative expression of the NR2B m RNA in the each dose group of Shugan Hewei decoction and the NAc region of the fluoxetine group increased, and the model was higher than that of the model group. The comparative difference between the group and the group was statistically significant (P0.01), and the relative expression of NR2B m RNA in the NAc region of the Shugan Hewei decoction group was higher than that of the fluoxetine group, the difference was statistically significant (P0.01). Experiment five: the effect of Shugan Hewei decoction on the PSD95 and NR2B expression in the NAc region of the depression model rats (1) the PSD95 relative expression in the NAc area of the model group was lower than that in the blank group. The relative expression of PSD95 in each dose group of Shugan Hewei decoction and fluoxetine group was higher than that in the model group (P0.01), and the relative expression of PSD95 in the high dose group was higher than that in the fluoxetine group (P0.01), and the difference was statistically significant (P0.01), and the low dose group was compared with the fluoxetine group. The difference was not statistically significant (P0.05). (2) the relative expression of NR2B in the NAc area of the model group was reduced, and the difference was statistically significant (P0.01), and the relative expression of NR2B in each dose group of Shugan Hewei decoction and the group of fluoxetine was higher than that in the model group (P0.01), of which the liver and stomach soup were low and the medium dose group NR2B was relatively expressed. The difference was significantly higher than that of fluoxetine group (P0.01). Conclusion 1. ancient doctors had a wide range of depression, including five transport and six qi stagnation, viscera depression and emotional depression. After the Ming and Qing Dynasties, the depression of depression was closely related to the "depression" of modern depression, which was closely related to the etiology and syndrome distribution of depression in the recent ten years. The study shows that emotional disorder is the main cause of depression, liver loss and catharsis are the core of its pathogenesis, and many viscera with influence and heart, spleen, stomach and other viscera are the pathological changes. The pathological changes of Qi and blood body fluid Yin and Yang disorders are its pathological changes. The treatment method is to dredge the liver to solve depression and regulate the pathological changes of the neuron in the PFC area caused by the.3. chronic stress, and the PFC-NAc-VTA nerve. The decrease of DA content, the increase of Glu content, the corresponding changes in the content of GABA, and the decrease of the expression of PSD95, NR2B and m RNA in the NAc region, may be the pathogenesis of depression, which may improve the depression state of the depression model rats, and reduce the damage of the neurons in the PFC area of the depression model rats. The abnormal increase or decline of DA, Glu, GABA content in the PFC-NAc-VTA nerve loop can reverse the abnormal downregulation of PSD95, NR2B and m RNA in the NAc region of the model rats, suggesting that the liver and stomach soup may be the.5. Chinese medicine "liver depression" that can play an antidepressant role in the PFC-NAc-VTA neural loop. The central mechanism may be related to the pathological changes of PFC neurons, abnormal expression of DA, Glu, GABA in PFC-NAc-VTA nerve circuit and synapse in NAc region.

【學(xué)位授予單位】：湖北中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R277.7

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