本文關(guān)鍵詞： MiRNA-30e 學(xué)習(xí)記憶 靜息態(tài)-功能磁共振 局部一致性 功能連接　出處：《山西醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:通過構(gòu)建Micro RNA-30e海馬過表達(dá)模型大鼠,觀察注射用丹參多酚酸對大鼠學(xué)習(xí)記憶功能的影響,并通過靜息態(tài)-功能磁共振技術(shù)在腦功能網(wǎng)絡(luò)層面探索注射用丹參多酚酸的作用機(jī)制。方法:1實驗分組:40只8周齡的雄性成年SD大鼠隨機(jī)分為Control組、Sham組、Micro RNA-30e過表達(dá)組(Model組)、注射用丹參多酚酸高劑量治療組(TSA high組)和注射用丹參多酚酸低劑量治療組(TSA low組),每組8只。2模型構(gòu)建:應(yīng)用腦立體定位儀進(jìn)行病毒轉(zhuǎn)染手術(shù),Control組不做任何處理,Sham組雙側(cè)海馬注射空載體病毒,Model組、TSA high組和TSA low組雙側(cè)海馬注射Micro RNA-30e載體病毒。3藥物干預(yù):造模2周后,TSA high組和TSA low組尾靜脈分別注射濃度2mg/ml和1mg/ml的注射用丹參多酚酸藥物溶液(10ml/Kg),Model組、Control組和Sham組同一時間尾靜脈注射生理鹽水(10ml/Kg)。4行為學(xué)檢測:給藥2周后,進(jìn)行Y迷宮和水迷宮行為學(xué)實驗。5影像學(xué)檢測:行為學(xué)實驗結(jié)束后,進(jìn)行靜息態(tài)-功能磁共振掃描,分析海馬“局部一致性”和“功能連接”。結(jié)果:1 Y迷宮自發(fā)交替實驗中,Model組大鼠的工作記憶較Control組顯著下降,而TSA high組工作記憶較Model組顯著提高:與Control組相比,Model組大鼠的自發(fā)交替正確率顯著減低(F(1,7)=34.68,P0.01);與Model組相比,TSA high組自發(fā)交替正確率提高(F(1,7)=23.75,P0.05),而TSA low組與Model組相比無顯著差異。各組之間的總進(jìn)臂次數(shù)無統(tǒng)計學(xué)差異。2 Morris水迷宮實驗中,Model組大鼠的長時記憶較Control組顯著下降,而TSA high組長時記憶較Model組顯著提高:在定位巡航實驗中,各組大鼠1-5天逃避潛伏期均逐漸下降,與Control組相比,Model組大鼠第3-5天逃避潛伏期顯著延長(F(4,28)=20.46,P0.001);與Model組相比,TSA high組大鼠第3-5天逃避潛伏期顯著減少(F(4,28)=8.136,P0.001);與Model組相比,TSA low組3-5天逃避潛伏期顯著減少(F(4,28)=5.616,P0.01)。在探索實驗中,與Control組相比,Model組大鼠平均跨臺次數(shù)顯著減少(F(1,7)=6.632,P0.05);與Model組相比,TSA high組大鼠平均跨臺次數(shù)顯著增多(F(1,7)=7.097,P0.05);與Model組相比,TSA low組大鼠平均跨臺次數(shù)無顯著差異。各組之間平均游泳速度無顯著差異。3局部一致性結(jié)果顯示:Model組與Control組相比,大鼠海馬區(qū)的Re Ho值為負(fù)值(FDR,P0.05);TSA high組與Model組相比,大鼠海馬區(qū)的Re Ho值增高(FDR,P0.05),而TSA low組與Model組相比,海馬區(qū)Re Ho值無顯著差異。4功能連接結(jié)果顯示:Model組與Control組相比,大鼠海馬與扣帶回的功能連接減低(FDR,P0.05);TSA high組與Model組相比,大鼠海馬與扣帶回的功能連接增強(qiáng)(FDR,P0.05),而TSA low組與Model組相比,海馬與扣帶回的功能連接無顯著差異。結(jié)論:Micro RNA-30e過表達(dá)可能降低了海馬局部一致性及與扣帶回的功能連接進(jìn)而引起了大鼠認(rèn)知功能損害。而注射用丹參多酚酸能夠提高海馬的局部一致性,并增強(qiáng)海馬與扣帶回的功能連接,這可能是其改善大鼠認(rèn)知功能的作用機(jī)制。
[Abstract]:Objective: to investigate the effects of salvia miltiorrhiza polyphenolic acid on learning and memory function of Micro RNA-30e model rats. The mechanism of salvia miltiorrhiza polyphenolic acid for injection was explored at the brain functional network level by resting state functional magnetic resonance technique. Forty 8-week-old male adult SD rats were randomly divided into Control group. Sham group (Sham group). Salvia miltiorrhiza polyphenolic acid high dose treatment group (TSA high group) and salvia polyphenolic acid injection low dose treatment group (TSA low group). The model of 8 rats in each group was constructed: the control group was transfected with the virus by stereotactic locator without any treatment. The model group of bilateral hippocampal injection of empty vector virus was used in the Sham group. TSA high group and TSA low group were injected with Micro RNA-30e carrier virus 3 drug in bilateral hippocampus: 2 weeks later. TSA high group and TSA low group were injected with 2 mg / ml and 1 mg / ml Salvia miltiorrhiza polyphenolic acid solution respectively. Behavioral examination of Control group and Sham group at the same time after intravenous injection of normal saline 10 ml / kg 4: 2 weeks after administration. The Y-maze and water-maze behavioral experiments were examined by 5 imaging. After the behavioral experiment was finished, the rest state functional magnetic resonance imaging (fMRI) was performed. The results showed that the working memory of the rats in the Control group was significantly lower than that in the Control group. However, the working memory of TSA high group was significantly higher than that of Model group. Compared with Control group, the correct rate of spontaneous alternation of TSA high group was significantly lower than that of Model group. (3) 4. 68% P0. 01 (P0. 01); Compared with Model group, the correct rate of spontaneous alternation in TSA high group was higher than that in Model group (23. 75% P 0. 05). However, there was no significant difference between TSA low group and Model group. There was no significant difference in the total arm entry times between the groups. 2. 2 Morris water maze test. The long-term memory of Model group was significantly lower than that of Control group, while that of TSA high group was significantly higher than that of Model group. The escape latency of rats in each group decreased gradually from 1-5 days to 5 days. Compared with the Control group, the escape latency of the rats in the Control group on the 3-5 days was significantly longer than that in the Control group. P0.001; Compared with the Model group, the escape latency of the rats in the TSA high group decreased significantly on the 3-5 day. Compared with Model group, the escape latency of TSA low group decreased significantly in 3-5 days. Compared with the Control group, the average number of transmissions in the Control group was significantly reduced to 6.632% (P 0.05). Compared with the Model group, the average number of transmissions in the TSA high group was significantly higher than that in the TSA high group. Compared with Model group. There was no significant difference in the average number of transmissions between the TSA low group and the Control group, but there was no significant difference in the average swimming speed among the three groups. 3 the results showed that there was no significant difference between the two groups. The value of re Ho in hippocampus of rats was negative. The value of re Ho in hippocampus of TSA high group was higher than that of Model group, while that of TSA low group was higher than that of Model group. There was no significant difference in re Ho value in hippocampus. 4 the results of functional connection showed that the functional connections between hippocampus and cingulate gyrus of rats in the w model group were lower than those in the Control group. The functional connections between hippocampus and cingulate gyrus were enhanced in TSA high group compared with Model group, while TSA low group was compared with Model group. There was no significant difference in functional connections between hippocampus and cingulate gyrus. The overexpression of RNA-30e may decrease the local consistency of hippocampus and the functional connection with cingulate gyrus, and then cause cognitive impairment in rats. However, salvia miltiorrhiza for injection can improve the local consistency of hippocampus. And enhance the functional connection between hippocampus and cingulate gyrus, which may be the mechanism of improving cognitive function in rats.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.1

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