本文選題：哺乳期 + SSRI�。� 參考：《昆明醫(yī)科大學(xué)》2016年碩士論文

【摘要】：[目的]本實(shí)驗(yàn)通過(guò)建立哺乳期使用氟西汀大鼠動(dòng)物模型,模擬發(fā)育期高血5-羥色胺自閉癥動(dòng)物模型,觀察哺乳期使用氟西汀對(duì)子代大鼠行為學(xué)、5-羥色胺能神經(jīng)元環(huán)路功能的影響,從而探討哺乳期使用SSRI類抗抑郁藥對(duì)子代行為學(xué)影響及其可能的病理生理機(jī)制,以期為自閉癥發(fā)病機(jī)制的研究提供理論依據(jù)。[方法]將SD妊娠大鼠隨機(jī)分成2組,每組各3只。待分娩后第5-21d予以實(shí)驗(yàn)組大鼠氟西汀(12mg/kg),對(duì)照組大鼠予以等量的生理鹽水,期間正常哺乳。嬰兒期分別測(cè)量子代大鼠體重、毛發(fā)、睜眼、聽覺和自由懸掛實(shí)驗(yàn)情況。待子代出生后第21天斷奶并將雌雄大鼠分籠飼養(yǎng)。兒童期子代大鼠行埋藏食物小球?qū)嶒?yàn)和曠場(chǎng)試驗(yàn)。兒童期(P35d)和青年期(P75d)分別取材行Western-Blot、IHC、IF檢測(cè)子代大鼠前額皮質(zhì)和中縫核SERT及TPH的含量。同時(shí),應(yīng)用ELISA技術(shù)檢測(cè)兒童期和青年期前額皮質(zhì)和中縫核5-HT含量。[結(jié)果]一、行為學(xué)實(shí)驗(yàn)結(jié)果：1.體重：與對(duì)照組相比,氟西汀組體重9d,11d,13d均較對(duì)照組明顯降低,有顯著性差異(P0.05)；2.毛發(fā)：與對(duì)照組相比,氟西汀組毛發(fā)長(zhǎng)度9d,11d無(wú)明顯降低,沒有顯著性差異(P0.05)。在13d實(shí)驗(yàn)組與對(duì)照組相比明顯降低,有顯著性差異(P0.05)：3.睜眼：13d氟西汀組與對(duì)照組相比睜眼程度無(wú)明顯改變(P0.05)；4.聽覺：與對(duì)照組相比,氟西汀組聽覺敏感性9d,11d明顯增加,有顯著性差異(P0.01)。13d實(shí)驗(yàn)組與對(duì)照組相比聽覺敏感性無(wú)明顯增加,無(wú)顯著性差異(P0.05)；5.埋藏食物小球?qū)嶒?yàn)：與對(duì)照組相比,氟西汀組仔鼠埋藏食物小球?qū)嶒?yàn)時(shí)間26d無(wú)明顯改變,無(wú)顯著性差異(P0.05)；6.自由懸掛實(shí)驗(yàn)：與對(duì)照組相比,氟西汀組自由懸掛實(shí)驗(yàn)時(shí)間在1ld,13d均明顯減少,有顯著性差異(P0.01)；7.曠場(chǎng)實(shí)驗(yàn)：與對(duì)照組相比,氟西汀組大便粒數(shù)在28d,29d,30d,31d均明顯增加,有顯著性差異(P0.01)；氟西汀組大便粒數(shù)平均值也有顯著性差異(P0.01)。二、免疫印跡、免疫組化、免疫熒光法檢測(cè)前額皮質(zhì)和中縫核SERT和TPH蛋白；酶聯(lián)免疫吸附法檢測(cè)前額葉皮質(zhì)和中縫核5-HT的含量：1.應(yīng)用Western-blot、IHC、IF技術(shù)檢測(cè)兒童期(35d)和青年期(75d) SERT蛋白在前額皮質(zhì)和中縫核表達(dá),結(jié)果發(fā)現(xiàn)：與哺乳期鹽水暴露組相比,FLX暴露組兒童期和青年期SERT蛋白表達(dá)明顯下調(diào),有顯著性差異(P0.05)。2.應(yīng)用Western-blot、IHC、IF技術(shù)檢測(cè)兒童期(35d)和青年期(75d)TPH蛋白在前額皮質(zhì)和中縫核表達(dá),結(jié)果發(fā)現(xiàn)：與哺乳期鹽水暴露組子代相比,FLX暴露組兒童TPH蛋白表達(dá)明顯下調(diào),有顯著性差異(P0.05)。3.應(yīng)用IF技術(shù)檢測(cè)仔鼠前額皮質(zhì)神經(jīng)元軸突及數(shù)目,結(jié)果發(fā)現(xiàn)：氟西汀暴露組仔鼠兒童期(35d)和青年期(75d)前額葉皮質(zhì)神經(jīng)元數(shù)量和軸突明顯減少。4.酶聯(lián)免疫吸附法檢測(cè)5-HT在前額葉皮質(zhì)和中縫核含量,結(jié)果發(fā)現(xiàn)：與對(duì)照組相比,兒童期(35d)氟西汀組5-HT在大腦總含量明顯增高,有顯著性差異(P0.01)；嬰兒期(75d)氟西汀組5-HT在前額皮質(zhì)和中縫核含量均明顯增高,有顯著性差異(P0.05)。[結(jié)論]1.哺乳期暴露于氟西汀導(dǎo)致子代的發(fā)育和行為異常。2.哺乳期暴露于氟西汀可通過(guò)下調(diào)子代大鼠前額皮質(zhì)和中縫核中TPH、SERT蛋白表達(dá)提高5-HT含量。3.暴露于氟西汀子代腦組織5-HT含量升高,可能導(dǎo)致類自閉行為。4.哺乳期暴露于SSRIs類抗抑郁藥對(duì)子代大鼠行為學(xué)有顯著影響,這種影響可能是由5-羥色胺能神經(jīng)元系統(tǒng)紊亂所致。
[Abstract]:[Objective] to establish lactation rats fluoxetine animal models used by this experiment, simulated development stage of high blood 5- HT autism animal model, to observe the lactation of fluoxetine in offspring rats behavior, 5- serotonin can affect neuronal loop function, so as to explore the pathophysiological mechanism of lactation SSRI antidepressants on offspring the behavior and its possible effects, in order to provide theoretical basis for the study of autism. Methods: the pathogenesis of pregnant SD rats were randomly divided into 2 groups, 3 rats in each group. To be 5-21d after delivery to the rats of the experimental group of fluoxetine (12mg/kg), saline control group rats were given the same amount of normal period lactation. Infants were measured body weight, offspring rats hair, eyes, hearing and free hanging experiment. The offspring born twenty-first days after weaning and male rats were divided into the cage. The childhood rat offspring for burial The food pellet test and open field test (P35d). Childhood and adolescence (P75d) were performed at Western-Blot, IHC, IF content detection of offspring rat prefrontal cortex and dorsal raphe nucleus SERT and TPH. At the same time, the application of ELISA technology in detection of childhood and young adulthood prefrontal cortex and nuclear 5-HT content. The raphe a behavioral test results: 1. body weight: compared with the control group, fluoxetine group weight 9D, 11d, 13D were significantly lower than the control group, there was significant difference (P0.05); 2. hair: compared with the control group, fluoxetine group the length of hair 9D, 11d decreased significantly, no significant difference (P0.05) 13D. In the experimental group decreased significantly compared with the control group, there was significant difference (P0.05): 13D:3. and fluoxetine group compared with the control group had no obvious change in open degree (P0.05); 4. hearing: compared with the control group, fluoxetine group acouesthesia 9D, 11d increased significantly The difference (P0.01).13d experimental group compared with the control group without auditory sensitivity increased significantly, no significant difference (P0.05); 5. buried food pellet test: compared with the control group, fluoxetine group buried food pellet test time 26D had no significant change, no significant difference (P0.05); 6. free hanging experiment: Compared with the control group, fluoxetine group free suspension test at the time of 1ld, 13D were significantly decreased, there was significant difference (P0.01); 7. open field test: compared with the control group, fluoxetine group stool grain number in 28d, 29d, 30d, 31d were significantly increased, there was significant difference (P0.01); fluoxetine stool the average grain number had significant difference (P0.01. Two), Western blot, immunohistochemistry, detect the prefrontal cortex and dorsal raphe nucleus SERT and TPH protein by immunofluorescence method; the content of enzyme-linked immunosorbent assay in the prefrontal cortex and dorsal raphe nucleus 5-HT: 1. Western-blot, IH C, detection of children during the period of IF Technology (35d) and youth (75D) the results showed that SERT protein expression in cortex, raphe nuclei and forehead: compared with lactation saline exposed group, FLX exposure during childhood and adolescence group expression of SERT protein decreased obviously, there was significant difference (P0.05).2. by Western-blot, IHC children, detection technology of IF (35d) and youth (75D) results showed that expression of TPH protein in the cortex, and raphe nuclei: forehead and lactation saline exposed offspring compared to FLX group of children exposed expression of TPH protein decreased obviously, there was significant difference (P0.05).3. IF was used to detect rat prefrontal cortex and the number of axons, results showed that: fluoxetine exposure group children filial mice (35d) and youth (75D) and the number of axons in the prefrontal cortex neurons significantly reduced.4. enzyme-linked immunosorbent assay for detection of 5-HT was found in the prefrontal cortex and the dorsal raphe nucleus and the content: According to groups of childhood (35d) fluoxetine group 5-HT significantly increased total content in the brain, there was significant difference (P0.01); infants (75D) fluoxetine group 5-HT were significantly higher in the prefrontal cortex and dorsal raphe nucleus content, there was significant difference (P0.05). Conclusion]1. lactational exposure to fluoxetine in offsprings the development and abnormal behavior of.2. lactational exposure to fluoxetine by tone generation rat prefrontal cortex and dorsal raphe nucleus in TPH, the expression of SERT protein increased the content of 5-HT.3. exposed to fluoxetine 5-HT content generation in brain tissue increased, may lead to autism behavior class.4. lactational exposure to SSRIs antidepressants in offspring rats behavior learn to have a significant effect, the effect may be caused by 5- serotonergic neuron system disorders.

【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.94

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