本文選題：逍遙散 + 抑郁癥��； 參考：《廣州中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：目的:觀察逍遙散對慢性輕度不可預(yù)知應(yīng)激誘導(dǎo)的抑郁癥模型大鼠行為學(xué)、犬尿氨酸代謝產(chǎn)物及海馬相關(guān)指標(biāo)的影響,初步探討逍遙散抗抑郁的作用機制,進一步驗證逍遙散的抗抑郁療效,為抑郁癥的診斷和治療提供客觀評價指標(biāo),為天然抗抑郁藥物奠定理論基礎(chǔ)和實驗依據(jù)。方法:SD雄性大鼠30只,隨機分為5個組,健康空白對照組+生理鹽水(normal,0.9%NS)、抑郁模型組+生理鹽水(model,0.9%NS),模型+帕羅西汀陽性對照組(Paroxetine,10mg/kg),模型+逍遙散水煎劑高劑量組(XYS-high,10.53g/kg)、模型+逍遙散水煎劑低劑量組(XYS-low,5.265 g/kg)。除空白對照組外,其余各組孤養(yǎng)并每日隨機給予一到兩種刺激,制備慢性不可預(yù)見性(CUMS)大鼠模型。造模4 w后給藥2 w,在造模的同時給予實驗藥物,根據(jù)大鼠個體體重胃灌相應(yīng)藥量。通過體重、攝食量、強迫游泳實驗、曠場實驗等指標(biāo)的測定評估逍遙散對抑郁模型大鼠的影響,于造模前、造模第10、20、28、42 d采集血樣,第43 d處死大鼠,快速剝離海馬體。采用液相色譜串聯(lián)質(zhì)譜法(LC-MS/MS)檢測大鼠血漿中色氨酸(TRP)、犬尿氨酸(KYN)、喹啉酸(QUIN)含量的變化;采用實時熒光定量法(Real-time qPCR)考察腦源性神經(jīng)營養(yǎng)因子(BDNF)、轉(zhuǎn)錄因子環(huán)磷腺苷反應(yīng)元件結(jié)合蛋白(CREB)及神經(jīng)細(xì)胞黏附分子(NCAM)3種可塑性相關(guān)蛋白mRNA表達;采用蛋白質(zhì)印跡法(Western Blot)考察海馬中上述蛋白表達的變化。結(jié)果:從行為學(xué)結(jié)果來看,與正常組相比,CUMS抑郁癥大鼠表現(xiàn)出自主活動顯著減少,游泳不動時間增加,體重和攝食量下降等,有顯著性差異(P0.01);逍遙散治療后大鼠自主活動、體重和攝食量、游泳不動時間均有所恢復(fù),統(tǒng)計結(jié)果有顯著性差異(P0.01)。行為學(xué)結(jié)束后,LC-MS/MS檢測結(jié)果顯示,與正常組相比,第28d模型組大鼠血漿中犬尿氨酸、喹啉酸的濃度降低,有顯著性差異(P0.01);逍遙散組與帕羅西汀組治療后大鼠血漿犬尿氨酸的含量有升高趨勢,但無統(tǒng)計學(xué)意義(P0.05),逍遙散高劑量組治療后大鼠血漿喹啉酸的含量明顯升高(P0.01)。與正常組相比,模型組大鼠海馬中CREB、BDNFmRNA的表達均降低,差異有統(tǒng)計學(xué)意義(P0.05),NCAM的蛋白表達顯著降低(P0.01);逍遙散高劑量組可使海馬組織中的BDNF mRNA表達升高,差異有統(tǒng)計學(xué)意義(P0.05)。與正常組相比,模型組大鼠海馬組織中NCAM(P0.05)、CREB(P0.01)蛋白表達減少,BDNF無明顯差異(P0.05);給藥后,與模型組相比,逍遙散組均能使NCAM蛋白表達顯著降低,CREB和BDNF蛋白表達顯著升高,統(tǒng)計結(jié)果有顯著性差異(P0.01)。結(jié)論:逍遙散對抑郁模型大鼠表現(xiàn)出明顯的抗抑郁作用,其調(diào)節(jié)了犬尿氨酸代謝異常,提高了犬尿氨酸和喹啉酸的含量,并上調(diào)了慢性應(yīng)激抑郁大鼠海馬BDNF和CREB的蛋白表達,下調(diào)NCAM的蛋白表達,增加BDNF陽性神經(jīng)元數(shù)量,改善神經(jīng)元形態(tài)。逍遙散治療抑郁癥可能是通過改善大鼠犬尿氨酸代謝功能及保護海馬神經(jīng)元作用,但其確切機制如何還有待進一步研究。
[Abstract]:Objective : To observe the effect of Xiaoyao Powder on the behavior , urinary protein metabolism and hippocampus related indexes of depression model induced by chronic mild unpredictable stress . The mechanism of Xiaoyao Powder ' s anti - depression was discussed . It provided an objective evaluation index for the diagnosis and treatment of depression . The model was divided into five groups : normal saline ( normal , 0.9 % NS ) , model + paroxitin positive control group ( group XYS - high , 10.53 g / kg ) , model + Xiaoyao powder decoction dose group ( XYS - low , 5.265 g / kg ) . The results showed that compared with the normal group , there was a significant difference in the levels of urinary and quinoline acids in the plasma of rats . The levels of CREB and BDNFmRNA in the hippocampus of the model group were significantly lower than those in the normal group ( P0.05 ) . Compared with the normal group , the expression of BDNF and CREB in the hippocampus of the model group was significantly lower than that of the normal group ( P0.05 ) . Conclusion : Xiaoyao Powder can significantly decrease the expression of BDNF and CREB in the hippocampus of the rats . The results show that the Xiaoyao Powder can improve the protein expression of BDNF and CREB in the hippocampus of the chronic stress depression rats , increase the number of BDNF positive neurons and improve the neuronal morphology .

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R285.5
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本文編號：1734579