注射用丹参多酚酸对MicroRNA-30e海马过表达大鼠认知功能及脑功能网络改变的影响

发布时间：2018-01-27 13:40

本文关键词： MiRNA-30e 学习记忆静息态-功能磁共振局部一致性功能连接　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:通过构建Micro RNA-30e海马过表达模型大鼠,观察注射用丹参多酚酸对大鼠学习记忆功能的影响,并通过静息态-功能磁共振技术在脑功能网络层面探索注射用丹参多酚酸的作用机制。方法:1实验分组:40只8周龄的雄性成年SD大鼠随机分为Control组、Sham组、Micro RNA-30e过表达组(Model组)、注射用丹参多酚酸高剂量治疗组(TSA high组)和注射用丹参多酚酸低剂量治疗组(TSA low组),每组8只。2模型构建:应用脑立体定位仪进行病毒转染手术,Control组不做任何处理,Sham组双侧海马注射空载体病毒,Model组、TSA high组和TSA low组双侧海马注射Micro RNA-30e载体病毒。3药物干预:造模2周后,TSA high组和TSA low组尾静脉分别注射浓度2mg/ml和1mg/ml的注射用丹参多酚酸药物溶液(10ml/Kg),Model组、Control组和Sham组同一时间尾静脉注射生理盐水(10ml/Kg)。4行为学检测:给药2周后,进行Y迷宫和水迷宫行为学实验。5影像学检测:行为学实验结束后,进行静息态-功能磁共振扫描,分析海马“局部一致性”和“功能连接”。结果:1 Y迷宫自发交替实验中,Model组大鼠的工作记忆较Control组显著下降,而TSA high组工作记忆较Model组显著提高:与Control组相比,Model组大鼠的自发交替正确率显著减低(F(1,7)=34.68,P0.01);与Model组相比,TSA high组自发交替正确率提高(F(1,7)=23.75,P0.05),而TSA low组与Model组相比无显著差异。各组之间的总进臂次数无统计学差异。2 Morris水迷宫实验中,Model组大鼠的长时记忆较Control组显著下降,而TSA high组长时记忆较Model组显著提高:在定位巡航实验中,各组大鼠1-5天逃避潜伏期均逐渐下降,与Control组相比,Model组大鼠第3-5天逃避潜伏期显著延长(F(4,28)=20.46,P0.001);与Model组相比,TSA high组大鼠第3-5天逃避潜伏期显著减少(F(4,28)=8.136,P0.001);与Model组相比,TSA low组3-5天逃避潜伏期显著减少(F(4,28)=5.616,P0.01)。在探索实验中,与Control组相比,Model组大鼠平均跨台次数显著减少(F(1,7)=6.632,P0.05);与Model组相比,TSA high组大鼠平均跨台次数显著增多(F(1,7)=7.097,P0.05);与Model组相比,TSA low组大鼠平均跨台次数无显著差异。各组之间平均游泳速度无显著差异。3局部一致性结果显示:Model组与Control组相比,大鼠海马区的Re Ho值为负值(FDR,P0.05);TSA high组与Model组相比,大鼠海马区的Re Ho值增高(FDR,P0.05),而TSA low组与Model组相比,海马区Re Ho值无显著差异。4功能连接结果显示:Model组与Control组相比,大鼠海马与扣带回的功能连接减低(FDR,P0.05);TSA high组与Model组相比,大鼠海马与扣带回的功能连接增强(FDR,P0.05),而TSA low组与Model组相比,海马与扣带回的功能连接无显著差异。结论:Micro RNA-30e过表达可能降低了海马局部一致性及与扣带回的功能连接进而引起了大鼠认知功能损害。而注射用丹参多酚酸能够提高海马的局部一致性,并增强海马与扣带回的功能连接,这可能是其改善大鼠认知功能的作用机制。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.1

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