發(fā)布時(shí)間：2018-05-08 23:01

  本文選題：肝郁證 + PolyI:C��； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的建立PolyI:C誘導(dǎo)小鼠肝郁證模型,探討逍遙散對(duì)PolyI:C誘導(dǎo)小鼠肝郁模型的作用及其作用機(jī)制。方法1.PolyI:C誘導(dǎo)小鼠肝郁證模型的建立:第一批:將40只C57小鼠隨機(jī)分為4組,對(duì)照組、3mg/kg PolyI:C組、6mg/kgPolyI:C組、12mg/kgPolyI:C組。除對(duì)照組外,其余三組予腹腔注射相應(yīng)濃度的PolyI:C溶液,用藥1天。第二批:將20只C57小鼠隨機(jī)分為2組,對(duì)照組、12 mg/kg Poly I:C造模組。造模組予腹腔注射12 mg/kg Poly I:C溶液,對(duì)照組予腹腔注射生理鹽水,連續(xù)3周。第三批:將60只C57小鼠隨機(jī)分為6組,對(duì)照組、模型組、逍遙散低、中、高劑量組、艾司西酞普蘭組。除對(duì)照組外,其余三組予腹腔注射PolyI:C,在造模前30分鐘予灌胃給藥,每天1次,連續(xù)3周。2.動(dòng)物模型的評(píng)價(jià)在造模后運(yùn)用曠場(chǎng)實(shí)驗(yàn)、糖水偏好實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn)、懸尾實(shí)驗(yàn)等評(píng)價(jià)行為學(xué)指標(biāo)。3.動(dòng)物組織樣品的采集與檢測(cè)在完成造模和行為學(xué)實(shí)驗(yàn)后,將小鼠麻醉,經(jīng)心臟采血后進(jìn)行灌注,并采集小鼠大腦組織,用于免疫熒光分析、免疫印跡和酶聯(lián)免疫測(cè)定。結(jié)果1.高劑量PolyI:C連續(xù)3周造模能成功建立小鼠肝郁證模型。與對(duì)照組比較,12 mg/kg PolyI(C組的小鼠中央?yún)^(qū)域停留時(shí)間明顯減少(P0.05),糖水偏好分?jǐn)?shù)明顯下降(P0.05),懸尾實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)的不動(dòng)時(shí)間延長(P0.05)。2.逍遙散能改善PolyI:C誘導(dǎo)的小鼠抑郁樣行為。與模型組比較,高劑量逍遙散組糖水偏好分?jǐn)?shù)顯著升高(P0.05),懸尾實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)的不動(dòng)時(shí)間明顯減少(P0.05)。3.逍遙散能調(diào)節(jié)PolyI:C誘導(dǎo)的前額皮質(zhì)、VTA、NAc炎癥細(xì)胞因子。與模型組比較,高劑量逍遙散和西酞普蘭均能降低前額皮質(zhì)顯著升高的IL-1β、IL-6及TNF-α的水平(P0.05);高劑量逍遙散可以降低VTA顯著升高的IL-6水平(P0.05),而西酞普蘭能下調(diào)IL-1β、IL-6及TNF-α的水平(P0.05);高劑量逍遙散和西酞普蘭均能降低NAc顯著升高的IL-6及TNF-α水平(P0.05)。4.逍遙散能下調(diào)PolyI:C造模后小鼠前額皮質(zhì)、VTA、NAc升高的小膠質(zhì)細(xì)胞數(shù)。與模型組比較,高劑量逍遙散和西酞普蘭能下調(diào)前額皮質(zhì)中顯著升高的小膠質(zhì)細(xì)胞數(shù)(P0.05);高劑量逍遙散和艾司西酞普蘭能下調(diào)VTA顯著升高的小膠質(zhì)細(xì)胞數(shù)(P0.05),西酞普蘭還能下調(diào)VTA升高的星型膠質(zhì)細(xì)胞數(shù)(P0.05);高劑量逍遙散和西酞普蘭能下調(diào)NAc顯著升高的小膠質(zhì)細(xì)胞數(shù)(P0.05)。5.逍遙散改善PolyI:C誘導(dǎo)肝郁證的作用可能與調(diào)節(jié)IDO、p38、GCH1蛋白的表達(dá)有關(guān)。在前額皮質(zhì)中,IDO和p38表達(dá)升高,逍遙散和西酞普蘭能下調(diào)其表達(dá)。在V,TA中,GCH1表達(dá)升高,逍遙散和西酞普蘭均能下調(diào)其表達(dá)。在NAc中,p38、GCH1表達(dá)升高,逍遙散能下調(diào)GCH1表達(dá),西酞普蘭能下調(diào)p38、GCH1表達(dá)。結(jié)論逍遙散對(duì)PolyI:C誘導(dǎo)的肝郁證小鼠具有預(yù)防性抗抑郁和抗神經(jīng)炎癥作用。長期使用PolyI:C能誘導(dǎo)小鼠大腦前額皮質(zhì)、VTA、NAc腦區(qū)產(chǎn)生神經(jīng)炎癥反應(yīng),這些改變能被逍遙散所改善。逍遙散對(duì)PolyI:C誘導(dǎo)肝郁證的抗抑郁作用可能與調(diào)節(jié)IDO、p38、GCH1蛋白表達(dá)有關(guān)。
[Abstract]:Objective to establish the model of liver depression induced by PolyI:C in mice and to explore the effect and mechanism of Xiaoyao Powder on the model of liver depression induced by PolyI:C in mice. Methods the model of liver depression induced by 1.PolyI:C in mice was established. The first batch: 40 C57 mice were randomly divided into 4 groups. The control group was divided into 3 mg / kg PolyI:C group and 6 mg / kg polyI: C group with 12 mg / kg polyi: C group. In addition to the control group, the other three groups were given intraperitoneal injection of corresponding concentration of PolyI:C solution for 1 day. The second batch: 20 C57 mice were randomly divided into two groups, the control group was treated with 12 mg/kg Poly I: C model. The model group was intraperitoneally injected with 12 mg/kg Poly I: C solution and the control group was treated with saline for 3 weeks. The third batch: 60 C57 mice were randomly divided into 6 groups: control group, model group, low, medium, high dose group and Escitalopram group. In addition to the control group, the other three groups were intraperitoneally injected with PolyI: C and given intragastric administration 30 minutes before modeling, once a day for 3 weeks. The animal model was evaluated with open field experiment, sugar water preference test, forced swimming test, tail suspension test and so on. The collection and detection of animal tissue samples after the completion of model and behavioral experiments, the mice were anesthetized and perfused with blood collected from the heart. The brain tissues of the mice were collected for immunofluorescence analysis, immunoblotting and enzyme-linked immunosorbent assay (Elisa). Result 1. The model of liver depression in mice was successfully established by high dose PolyI:C for 3 weeks. Compared with the control group, the retention time in the central area of the mice in 12 mg/kg PolyI(C group decreased significantly, the preference fraction of sugar water decreased significantly, and the immobility time of tail suspension test and forced swimming test was prolonged (P0.05 路2). Xiaoyao Powder can improve the depressive behavior induced by PolyI:C in mice. Compared with the model group, the sugar water preference fraction in the high dose Xiaoyao powder group was significantly higher than that in the model group, and the immobility time of the tail suspension test and forced swimming test was significantly decreased. Xiaoyao Powder can regulate the inflammatory cytokines of VTA-NAc in prefrontal cortex induced by PolyI:C. Compared with the model group, Both high dose Xiaoyao Powder and citalopram could decrease the levels of IL-1 尾 -IL-6 and TNF- 偽 in the prefrontal cortex, and high dose Xiaoyao Powder could decrease the IL-6 level of VTA, while citalopram could down-regulate the levels of IL-1 尾 -IL-6 and TNF- 偽 (P0.05), and high dose Xiaoyao San could decrease the level of IL-1 尾 -IL-6 and TNF- 偽 (P0.05). Both telecontrol and citalopram could decrease the levels of IL-6 and TNF- 偽, which were significantly increased in NAc. Xiaoyao Powder can down-regulate the increased number of microglia in prefrontal cortex of mice after PolyI:C model. Compared with the model group, High dose Xiaoyao San and citalopram could down-regulate the significantly increased microglial cell count in prefrontal cortex (P0.05), high dose Xiaoyao Powder and Escitalopram could down-regulate the number of microglia cells significantly increased in VTA, and citalopram could also down-regulate the increase of VTA. High dose of Xiaoyao San and citalopram could down-regulate the number of microglial cells significantly increased in NAc. The effect of Xiaoyao Powder on PolyI:C induced liver depression may be related to the regulation of the expression of GCH1 protein in IDOP38. In prefrontal cortex, the expression of IDO and p38 increased, but Xiaoyao San and citalopram could down-regulate the expression of IDO and p38. The expression of GCH1 in VTA was increased, and both Xiaoyao San and citalopram could down-regulate its expression. In NAc, the expression of p38 GCH1 was increased, the expression of GCH1 was down-regulated by Xiaoyao San, and the expression of p38 GCH1 was down-regulated by citalopram. Conclusion Xiaoyao Powder has preventive antidepressant and anti-inflammatory effects on PolyI:C induced liver depression mice. Long-term use of PolyI:C could induce neuroinflammatory responses in the prefrontal cortex of mice, and these changes could be improved by Xiaoyao San. The antidepressant effect of Xiaoyao Powder on PolyI:C induced liver depression may be related to regulating the expression of GCH1 protein in IDO p38.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5

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