8-OH-DPAT對青春期病理性攻擊大鼠前額葉皮層和海馬內(nèi)BDNF及GDNF的影響
發(fā)布時間：2018-10-05 10:14
【摘要】：目的探索8-OH-DPAT即五羥色胺(5-HT)1A受體激動劑對青春期病理性攻擊大鼠前額葉皮層、海馬內(nèi)腦源性神經(jīng)營養(yǎng)因子(BDNF)和膠質(zhì)源性神經(jīng)營養(yǎng)因子(GDNF)的影響,為進(jìn)一步探索病理性攻擊行為的生物學(xué)機(jī)制提供一定基礎(chǔ)。方法1實驗動物及分組購買雄性Sprague-Dawley(SD)大鼠56只(購于重慶醫(yī)科大學(xué)實驗動物中心,生后21天),隨機(jī)分成6組:實驗組(即模型組,n=7)、對照組(即空白對照組,n=7)、實驗藥物組(n=7)、實驗鹽水組(n=7)、對照藥物組(n=7)、對照鹽水組(n=7),剩余大鼠為入侵鼠(工具鼠)(n=14)。2青春期病理性攻擊大鼠模型建立及攻擊、神經(jīng)營養(yǎng)因子檢測從出生后21天開始,對實驗組、實驗藥物組及實驗鹽水組均采用國際通用早年慢性應(yīng)激方法建立病理性攻擊大鼠模型,應(yīng)激手段主要有孤養(yǎng)、晝夜顛倒、去獎賞挫敗、預(yù)激惹刺激和居住-入侵實驗,至出生后56天即青春期結(jié)束應(yīng)激。對照組、對照藥物組、對照鹽水組及入侵鼠均正常養(yǎng)育。建模完成后對上述6組采用居住-入侵實驗行攻擊行為檢測,檢測指標(biāo)包括攻擊潛伏期、攻擊要害部位、屈服后繼續(xù)攻擊。完成攻擊行為檢測后對實驗組、對照組斷頭取前額葉皮層、海馬行免疫印跡檢測BDNF、GDNF蛋白水平。3 8-OH-DPAT干預(yù)后攻擊、神經(jīng)營養(yǎng)因子檢測對實驗藥物組、對照藥物組腹腔注射兩周的8-OH-DPAT(0.5mg/kg),對實驗鹽水組、對照鹽水組腹腔注射兩周的生理鹽水(2ml/只)。攻擊、神經(jīng)營養(yǎng)因子檢測方法及指標(biāo)同前。結(jié)果1成功建模后攻擊、神經(jīng)營養(yǎng)因子檢測1.1攻擊行為:實驗組與對照組比較,實驗組攻擊潛伏期顯著縮短,差異有統(tǒng)計學(xué)意義(P0.01);實驗組攻擊要害部位和屈服后繼續(xù)攻擊顯著增加,差異具統(tǒng)計學(xué)意義(P0.01)。1.2神經(jīng)營養(yǎng)因子:免疫印跡檢測發(fā)現(xiàn):實驗組大鼠前額葉皮層BDNF、GDNF蛋白較對照組降低,差異有統(tǒng)計學(xué)意義(P0.01)。對于海馬內(nèi)BDNF及GDNF蛋白,實驗組亦較對照組降低,差異有統(tǒng)計學(xué)意義(P0.01)。2干預(yù)后攻擊、神經(jīng)營養(yǎng)因子檢測2.1干預(yù)后攻擊行為比較:2.1.1攻擊潛伏期:8-OH-DPAT干預(yù)后的實驗藥物組與實驗鹽水組相比,實驗藥物組大鼠攻擊潛伏期延長,差異具統(tǒng)計學(xué)意義(P0.05),而實驗鹽水組與對照鹽水組、實驗藥物組與對照藥物組、對照藥物組與對照鹽水組之間比較,差異均無統(tǒng)計學(xué)意義(P0.05)。2.1.2攻擊要害部位:實驗藥物組較實驗鹽水組明顯減少(P0.01),實驗鹽水組與對照鹽水組、實驗藥物組與對照藥物組、對照藥物組與對照鹽水組之間相比,差異均無統(tǒng)計學(xué)意義(P0.05)。2.1.3屈服后繼續(xù)攻擊:實驗鹽水組較對照鹽水組仍顯著增加(P0.01)、實驗藥物組較實驗鹽水組顯著降低(P0.01),對照藥物與對照鹽水組、實驗藥物與對照藥物比較,差異均無統(tǒng)計學(xué)意義(P0.05)。2.2干預(yù)后大鼠前額葉皮層和海馬內(nèi)神經(jīng)營養(yǎng)因子檢測2.2.1前額葉皮層:實驗鹽水組大鼠前額葉皮層內(nèi)BDNF、GDNF蛋白水平較對照鹽水組顯著降低(P0.01,P0.05),實驗藥物組較實驗鹽水組顯著增加(P0.01,P0.05)。對照藥物與對照鹽水、實驗藥物組與對照藥物組相比,差異無統(tǒng)計學(xué)意義(P0.05)。2.2.2海馬:對于海馬內(nèi)BDNF、GDNF蛋白,實驗鹽水組較對照鹽水組顯著降低(P0.01),實驗藥物組較實驗鹽水組增加,差異具統(tǒng)計學(xué)意義(P0.01)。對照藥物組與對照鹽水組、實驗藥物組與對照藥物組相比,差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論1青春期大鼠經(jīng)歷早年慢性應(yīng)激后可產(chǎn)生病理性攻擊。2經(jīng)歷早年慢性應(yīng)激后的青春期大鼠前額葉皮層及海馬內(nèi)的BDNF、GDNF蛋白水平降低,可能是其產(chǎn)生病理性攻擊行為的因子。3 5-HT1A受體激動劑,即8-OH-DPAT可上調(diào)前額葉皮層和海馬內(nèi)的BDNF、GDNF蛋白,并可在一定程度上減輕青春期大鼠的由早年慢性應(yīng)激引起的病理性攻擊行為。
[Abstract]:Objective To explore the effect of 8-OH-DPAT (5-HT) 1A receptor agonist on the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) and glial source neurotrophic factor (NPY) in the rat prefrontal cortex and hippocampus. It provides a foundation for further exploring the biological mechanism of pathological attack. Methods56 male Sprague-Dawley (SD) rats were randomly divided into 6 groups: experimental group (model group, n = 7), control group (control group, n = 7) and experimental group (n = 7). The experimental saline group (n = 7), control group (n = 7), control saline group (n = 7), the remaining rats were invading rat (tool rat) (n = 14). The experimental drug group and the experimental saline group were used to establish the pathological attack rat model by using the international general early-age chronic stress method, and the stress method was mainly solitary, day-and-night upside down, dereward frustration, pre-excitation stimulation and residence-invasion experiment, and the stress was terminated at 56 days after birth, that is, puberty. Control group, control group, control saline group and invasive mice were all normal. After the modeling is finished, the 6 groups are detected by the residential-intrusion experiment line attack, and the detection indexes include the attack latency, the attack key position and the yield, and then the attack is continued. The experimental group and the control group were divided into two groups: 8-OH-DPAT (0. 5mg/ kg), which was injected intraperitoneally with 8-OH-DPAT (0. 5mg/ kg). The control saline group was injected into the abdominal cavity for two weeks of normal saline (2ml/ only). and the detection method and the index of the attack and the neurotrophic factor are the same. Results 1. The attack latency of the experimental group was significantly shortened and the difference was statistically significant (P0.01). The difference was statistically significant (P 0.01). 1. 2 neurotrophic factor: The experimental group was found to have a statistically significant difference in BDNF and p27 protein in the prefrontal cortex of the experimental group (P0.01). Compared with the control group, there was statistical significance in the experimental group (P0.01). After the intervention, the nerve nutrition factor was detected by 2.1. The attack latency: 8-OH-DPAT intervention group was compared with the experimental saline group. In the experimental group, the latency of attack was prolonged and the difference was statistically significant (P0.05). The experimental saline group and the control saline group, the control group and the control group were not statistically significant (P0.05). Compared with the control saline group, there was no significant difference between the control group and the control saline group (P0.05). Compared with the control saline group, the saline group of the experimental group was significantly lower than that in the control saline group (P0.01). Compared with the control saline group, the experimental drug was compared with the control saline group. There was no statistical significance in the difference (P 0.05). 2. 2. The levels of BDNF and NPY in the prefrontal cortex of the experimental saline group were significantly lower than that in the control saline group (P <0.01, P 0.05). The experimental group was significantly higher than that in the saline group (P <0.01, P 0.05). Compared with the control saline group, the difference was not statistically significant (P0.05). The difference was statistically significant (P0.01). Compared with the control group, there was no significant difference between the control group and the control group (P0.05). Conclusion The level of BDNF and tau protein in the prefrontal cortex and hippocampus of adolescent rats after chronic stress in the early years may be a factor of pathological attack. The 5-HT1A receptor agonist, That is, 8-OH-DPAT can upregulate BDNF and p27 protein in the frontal cortex and hippocampus, and can reduce the pathological behavior induced by chronic stress in the early years of puberty.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749
本文編號：2252999
[Abstract]:Objective To explore the effect of 8-OH-DPAT (5-HT) 1A receptor agonist on the prefrontal cortex, the brain-derived neurotrophic factor (BDNF) and glial source neurotrophic factor (NPY) in the rat prefrontal cortex and hippocampus. It provides a foundation for further exploring the biological mechanism of pathological attack. Methods56 male Sprague-Dawley (SD) rats were randomly divided into 6 groups: experimental group (model group, n = 7), control group (control group, n = 7) and experimental group (n = 7). The experimental saline group (n = 7), control group (n = 7), control saline group (n = 7), the remaining rats were invading rat (tool rat) (n = 14). The experimental drug group and the experimental saline group were used to establish the pathological attack rat model by using the international general early-age chronic stress method, and the stress method was mainly solitary, day-and-night upside down, dereward frustration, pre-excitation stimulation and residence-invasion experiment, and the stress was terminated at 56 days after birth, that is, puberty. Control group, control group, control saline group and invasive mice were all normal. After the modeling is finished, the 6 groups are detected by the residential-intrusion experiment line attack, and the detection indexes include the attack latency, the attack key position and the yield, and then the attack is continued. The experimental group and the control group were divided into two groups: 8-OH-DPAT (0. 5mg/ kg), which was injected intraperitoneally with 8-OH-DPAT (0. 5mg/ kg). The control saline group was injected into the abdominal cavity for two weeks of normal saline (2ml/ only). and the detection method and the index of the attack and the neurotrophic factor are the same. Results 1. The attack latency of the experimental group was significantly shortened and the difference was statistically significant (P0.01). The difference was statistically significant (P 0.01). 1. 2 neurotrophic factor: The experimental group was found to have a statistically significant difference in BDNF and p27 protein in the prefrontal cortex of the experimental group (P0.01). Compared with the control group, there was statistical significance in the experimental group (P0.01). After the intervention, the nerve nutrition factor was detected by 2.1. The attack latency: 8-OH-DPAT intervention group was compared with the experimental saline group. In the experimental group, the latency of attack was prolonged and the difference was statistically significant (P0.05). The experimental saline group and the control saline group, the control group and the control group were not statistically significant (P0.05). Compared with the control saline group, there was no significant difference between the control group and the control saline group (P0.05). Compared with the control saline group, the saline group of the experimental group was significantly lower than that in the control saline group (P0.01). Compared with the control saline group, the experimental drug was compared with the control saline group. There was no statistical significance in the difference (P 0.05). 2. 2. The levels of BDNF and NPY in the prefrontal cortex of the experimental saline group were significantly lower than that in the control saline group (P <0.01, P 0.05). The experimental group was significantly higher than that in the saline group (P <0.01, P 0.05). Compared with the control saline group, the difference was not statistically significant (P0.05). The difference was statistically significant (P0.01). Compared with the control group, there was no significant difference between the control group and the control group (P0.05). Conclusion The level of BDNF and tau protein in the prefrontal cortex and hippocampus of adolescent rats after chronic stress in the early years may be a factor of pathological attack. The 5-HT1A receptor agonist, That is, 8-OH-DPAT can upregulate BDNF and p27 protein in the frontal cortex and hippocampus, and can reduce the pathological behavior induced by chronic stress in the early years of puberty.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749
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