SD大鼠认知障碍动物模型制作及机制研究

发布时间：2018-07-16 11:30

【摘要】：大脑海马与认知功能之间的关系一直都是研究热点,但其对内脏活动之间的影响知之甚少。临床特征上,老年痴呆患者往往伴有代谢水平异常,具资料报道,有高达81%的散发性老年痴呆患者出现不同程度的代谢异常特征。3-轻基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-Coenzyme Areductase,HMG-CR)是脂代谢的关键酶,本实验通过SD大鼠构建认知障碍动物模型,探讨海马认知障碍对血脂水平的影响及其与肝脏HMG-CR表达的关系,为脂代谢的深入研究提供实验依据。为探讨认知障碍大鼠血脂水平,采用Aβ1-42大鼠海马内注射构建认知障碍动物模型,全自动生化分析仪检测血脂水平。结果显示,实验组大鼠逃避潜伏期、跨越平台的次数、在原平台象限时间百分比分别为(75.19±2.24)s、(1.68±0.83)次、17.33%土4.75%与假手术组和对照组比较,均有显著性差异(P0.05)。实验组大鼠TG、TC、LDL分别为(2.30±0.08)mmol/L、(4.60±0.10)mmol/L、(2.41±0.06)mmol/L,与假手术组和对照组相比均显著升高(P0.05)。为探讨大鼠血脂水平变化是否与大鼠海马神经元凋亡有关,采用TUNEL法检测大鼠海马神经元凋亡,结果显示,实验组大鼠海马神经元凋亡指数为67.73土4.38%,假手术组和对照组分别为19.88±4.31%、16.45±5.50%,与实验组比较,均有显著性差异(P0.05)。为探讨认知障碍SD大鼠肝脏HMG-CR的表达情况,采用半定量反转录-聚合酶链反应法(RT-PCR)检测实验大鼠肝脏HMG-CRmRNA的表达,蛋白印迹法(Westem Blot)检测实验大鼠肝脏HMG-CR的表达。实验结果显示,实验组大鼠中肝脏HMG-CRmRNA的表达水平为0.49±0.03,明显高于假手术组和对照组(P0.05);实验组大鼠中肝脏HMG-CR的表达水平为0.50±0.02,显著高于假手术组与对照组(P0.05)。综上所述,Aβ1-42大鼠海马内注射可成功制备大鼠海马认知障碍模型,且海马认知障碍可引起实验大鼠血脂水平升高,这一机制可能与认知障碍实验大鼠肝脏HMG-CR的表达水平升高有关。
[Abstract]:The relationship between hippocampus and cognitive function has been a hot topic, but its influence on visceral activity is poorly understood. Clinically, Alzheimer's patients are often accompanied by abnormal metabolic levels, which have been reported. Up to 81% of the sporadic dementia patients had different metabolic characteristics. 3-hydroxy-3-methylglutaryl-Coenzyme reductase-A reductase (HMG-CR) was a key enzyme in lipid metabolism. A cognitive impairment model was established in SD rats. To investigate the effect of hippocampal cognitive impairment on serum lipids and its relationship with HMG-CR expression in liver, and to provide experimental evidence for the further study of lipid metabolism. In order to investigate the level of blood lipid in cognitive impaired rats, a rat model of cognitive impairment was established by intrahippocampal injection of A 尾 1-42 rats, and blood lipids were measured by automatic biochemical analyzer. The results showed that the percentage of escape latency and the times of crossing the platform in the original platform quadrant were (75.19 卤2.24) s, (1.68 卤0.83) times (17.33% 卤4.75%), which were significantly different from those in the sham operation group and the control group (P0.05). Compared with sham operation group and control group, the LDL levels of TGN TCU in experimental group were (2.30 卤0.08) mmol / L, (4.60 卤0.10) mmol / L and (2.41 卤0.06) mmol / L, significantly higher than those in sham operation group and control group (P0.05). In order to investigate whether the changes of serum lipids were related to the apoptosis of rat hippocampal neurons, Tunel method was used to detect the apoptosis of rat hippocampal neurons. The apoptotic index of hippocampal neurons was 67.73 卤4.38 in the experimental group, 19.88 卤4.31 in the sham operation group and 16.45 卤5.50 in the control group, respectively. There was significant difference between the experimental group and the experimental group (P0.05). In order to investigate the expression of HMG-CR in the liver of SD rats with cognitive impairment, the expression of HMG-CR mRNA was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the expression of HMG-CR was detected by Western blot. The results showed that the expression level of HMG-CR mRNA in liver of experimental group was 0.49 卤0.03, which was significantly higher than that of sham operation group and control group (P0.05), and that of liver HMG-CR in experimental group was 0.50 卤0.02, which was significantly higher than that in sham operation group and control group (P0.05). In conclusion, hippocampal cognitive impairment model of rats was successfully established by intrahippocampal injection of A 尾 1-42, and hippocampal cognitive impairment could induce the elevation of blood lipid level in experimental rats. This mechanism may be related to the increased expression of HMG-CR in the liver of experimental rats with cognitive impairment.
【学位授予单位】：广西大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R-332;R749.16

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