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(duì)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(jī)制,進(jìn)一步驗(yàn)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(píng)價(jià)指標(biāo),為天然抗抑郁藥物奠定理論基礎(chǔ)和實(shí)驗(yàn)依據(jù)。方法:SD雄性大鼠30只,隨機(jī)分為5個(gè)組,健康空白對(duì)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(yáng)性對(duì)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(duì)照組外,其余各組孤養(yǎng)并每日隨機(jī)給予一到兩種刺激,制備慢性不可預(yù)見(jiàn)性(CUMS)大鼠模型。造模4 w后給藥2 w,在造模的同時(shí)給予實(shí)驗(yàn)藥物,根據(jù)大鼠個(gè)體體重胃灌相應(yīng)藥量。通過(guò)體重、攝食量、強(qiáng)迫游泳實(shí)驗(yàn)、曠場(chǎng)實(shí)驗(yàn)等指標(biāo)的測(cè)定評(píng)估逍遙散對(duì)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(cè)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(shí)時(shí)熒光定量法(Real-time qPCR)考察腦源性神經(jīng)營(yíng)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(dá);采用蛋白質(zhì)印跡法(Western Blot)考察海馬中上述蛋白表達(dá)的變化。結(jié)果:從行為學(xué)結(jié)果來(lái)看,與正常組相比,CUMS抑郁癥大鼠表現(xiàn)出自主活動(dòng)顯著減少,游泳不動(dòng)時(shí)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(dòng)、體重和攝食量、游泳不動(dòng)時(shí)間均有所恢復(fù),統(tǒng)計(jì)結(jié)果有顯著性差異(P0.01)。行為學(xué)結(jié)束后,LC-MS/MS檢測(cè)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(shì),但無(wú)統(tǒng)計(jì)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(dá)均降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05),NCAM的蛋白表達(dá)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(dá)升高,差異有統(tǒng)計(jì)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(dá)減少,BDNF無(wú)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(dá)顯著降低,CREB和BDNF蛋白表達(dá)顯著升高,統(tǒng)計(jì)結(jié)果有顯著性差異(P0.01)。結(jié)論:逍遙散對(duì)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(dá),下調(diào)NCAM的蛋白表達(dá),增加BDNF陽(yáng)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(guò)改善大鼠犬尿氨酸代謝功能及保護(hù)海馬神經(jīng)元作用,但其確切機(jī)制如何還有待進(jìn)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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285.5
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本文編號(hào)：1734579