本文選題：抑郁大鼠 + 行為學(xué)��； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:初步研究干酪乳桿菌(Lactobacillus casei)對抑郁大鼠行為、神經(jīng)系統(tǒng)及腸道菌群的影響。方法:適應(yīng)性喂養(yǎng)后按體重,將大鼠隨機分為5組,分別是空白對照組(A),模型組(B),陽性對照組(C),干酪乳桿菌干預(yù)劑量I組(D)和干預(yù)劑量II組(E)組。除A組外,對其余各組在整個實驗中采用CUMS結(jié)合孤養(yǎng)建立大鼠抑郁模型。建模三周后采用灌胃的方法進行干預(yù),D、E組分別給予干酪乳桿菌4×108 CFU/kg/d和8×108 CFU/kg/d,C組給予帕羅西汀1.8 mg/kg/d,A組和B組給予等量的生理鹽水(1.8 mg/kg/d),干預(yù)時間為四周。采用曠場實驗、糖水消耗實驗、24 h食物消耗實驗及記錄體重變化,觀察大鼠行為學(xué)變化。干預(yù)結(jié)束后大鼠禁食不禁水12 h,注射3%戊巴比妥鈉麻醉,低溫下迅速分離大腦前額葉皮質(zhì),解剖留取盲腸內(nèi)容物,通過HPLC-ECD檢測皮質(zhì)中多巴胺(DA)、去甲腎上腺素(NE)和5-羥色胺(5-HT)的濃度,Western Blotting檢測腦源性神經(jīng)營養(yǎng)因子(BDNF)、p38MAPK和p ERK1/2蛋白的表達,RT-PCR檢測酪氨酸激酶受體B(Trk B)受體和N-甲基-D-天冬氨酸受體(NMDA)受體的NR1亞基的m RNA表達,RT-PCR檢測盲腸內(nèi)容物中糞腸球菌(Enterococcus faecalis)、雙歧桿菌屬(Bifidobacterium)、乳酸菌(Lactobacillus)和大腸桿菌(Escherichia coli)四種菌在各組間的差異。結(jié)果:在應(yīng)激下,大鼠表現(xiàn)出抑郁樣行為,糖水偏愛百分比、移動速率和距離B組較A組分別降低24.6%、37.6%和23.1%。干酪乳桿菌干預(yù)后大鼠的抑郁行為明顯改善,表現(xiàn)為糖水偏愛百分比在C、D、E組較B組分別顯著增加20.5%、15.9%、16.0%,差別有顯著性(P0.05);在曠場中的移動速率和移動距離均較B組均顯著增加(P0.05);從第四周開始,B組較A組和各干預(yù)組體重增長緩慢(P0.05),而食物消耗量在各組間未見明顯差異;CUMS使得大鼠前額葉皮質(zhì)中Trk B受體和NR1亞基的m RNA表達、BDNF蛋白表達及血漿DA、NE和5-HT的濃度顯著降低(P0.05),而干預(yù)后這一情況得到改善,其中與B組相比D、E組BDNF分別增加40.9%和42.9%,DA、NE、5-HT分別增加15.8%、15.5%、11.2%和20.5%、19.7%、11.7%。在CUMS暴露下大鼠前額葉皮質(zhì)中p38MAPK和p ERK1/2的蛋白表達水平顯著增加,即B組與A組相比,p38MAPK和p ERK1/2分別增加122%、65.7%和147%,而干預(yù)后能顯著逆轉(zhuǎn)這些變化,D、E組較B組分別降低23.2%、24.6%、46.9%和28.7%、29.7%、46.9%(P0.05)。應(yīng)激下B組與A組相比乳酸菌、糞腸球菌和大腸桿菌均顯著增加,差異均有統(tǒng)計學(xué)意義(P0.05),雙歧桿菌呈下降趨勢,但未見顯著性差異。干預(yù)后與B組相比乳酸菌、糞腸球菌和大腸桿菌在C、D、E組均顯著降低,差異均有統(tǒng)計學(xué)意義(P0.05),而雙歧桿菌呈上升趨勢,未見統(tǒng)計學(xué)差異。結(jié)論:在應(yīng)激下,大鼠表現(xiàn)出明顯的抑郁樣行為,而干酪乳桿菌能夠改善抑郁樣行為,影響大鼠神經(jīng)系統(tǒng),調(diào)節(jié)抑郁大鼠的腸道菌群,為抑郁癥的相關(guān)研究提供新的視角。
[Abstract]:Aim: to study the effects of Lactobacillus caseii on behavior, nervous system and intestinal flora in depressed rats. Methods: after adaptive feeding, rats were randomly divided into 5 groups according to their body weight. The rats were divided into 5 groups: blank control group, model group, positive control group, Lactobacillus casei intervention dose group I (D) and intervention dose group II (E) group. With the exception of group A, the depression model of rats was established by CUMS combined with solitude in the whole experiment. After three weeks of modeling, the rats in group E were treated with Lactobacillus casei 4 脳 10 ~ 8 CFU/kg/d and group C 8 脳 10 ~ 8 CFU / kg 路kg ~ (-1) 路d ~ (-1) respectively. Paroxetine 1.8 mg 路kg ~ (-1) 路d ~ (-1) of normal saline was given to group A and B for four weeks. Open field experiment, sugar water consumption test, food consumption test for 24 h and body weight change were used to observe the behavioral changes of rats. Rats fasting for 12 hours were anesthetized with 3% pentobarbital sodium. The prefrontal cortex was quickly separated under hypothermia and the caecum contents were dissected. The expression of BDNF p38 MAPK and p ERK1/2 protein in brain derived neurotrophic factor (BDNF) was detected by HPLC-ECD. The tyrosine kinase receptor (B(Trk B) receptor and N- methyl-D- (-) -day receptor were detected by reverse transcription-polymerase chain reaction (RT-PCR). The m RNA expression of NR1 subunit of aspartic acid receptor (NMDA) receptor was detected by reverse transcription-polymerase chain reaction (RT-PCR). Enterococcus faecalisus, Bifidobacterium, Lactobacillus (Lactobacillus) and Escherichia coli (Escherichia coli) in cecum contents were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results: under stress, rats showed depressive behavior, percentage of sugar water preference, moving rate and distance of group B decreased 24.637.6% and 23.1g than those of group A, respectively. After Lactobacillus casei intervention, the depressive behavior of rats was significantly improved. The results showed that the percentage of preference for sugar water in group C DU E was significantly higher than that in group B (20. 5%, P 0. 05%, P 0. 05), and that in group B was significantly higher than that in group B (P 0. 05), and from the fourth week onwards, group B was significantly higher than group A and the intervention group in terms of moving distance and velocity (P 0. 05%, P 0. 05%, P 0. 05%, P 0. 05%, P 0. 05%, P 0. 05%, respectively). There was no significant difference in food consumption among the three groups. The expression of m RNA of Trk B receptor and NR1 subunit in the prefrontal cortex of rats and the concentration of DANE and 5-HT in plasma decreased significantly in the prefrontal cortex of rats, but after intervention, the expression of m RNA in the prefrontal cortex of rats was significantly decreased. The situation has improved, Compared with group B, the BDNF of group D and E increased by 40.9% and 42.9%, respectively. The expression of p38MAPK and p ERK1/2 in prefrontal cortex of rats exposed to CUMS was significantly increased, that is to say, compared with group A, the levels of p38 MAPK and p ERK1/2 in group B were increased by 122. 7% and 14. 7%, respectively. After intervention, these changes were significantly reversed by 23. 224.646. 9% and 28. 729. 729. 7%, respectively. Under stress, lactic acid bacteria, Enterococcus faecalis and Escherichia coli in group B were significantly higher than those in group A, and the difference was statistically significant (P 0.05). Bifidobacterium showed a downward trend, but there was no significant difference. Compared with group B, lactic acid bacteria, Enterococcus faecalis and Escherichia coli decreased significantly in group C (P 0.05), but Bifidobacterium showed an increasing trend, but there was no statistical difference. Conclusion: under stress, rats showed depressive behavior, while Lactobacillus casei could improve depression-like behavior, affect nervous system, regulate intestinal flora of depressed rats, and provide a new perspective for the study of depression.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.4

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