右美托咪定对老龄大鼠体外循环术后认知功能的影响及可能机制研究
发布时间：2018-12-10 21:42
【摘要】：目的:术前使用右美托咪定对行体外循环手术的老龄大鼠术后认知功能的影响及可能机制的探讨。方法:18~20月龄健康雄性SD大鼠90只,随机分为实验组、对照组和右美组,每组30只,实验组大鼠腹腔注射生理盐水后进行体外循环手术,对照组大鼠不进行任何处理,右美组大鼠腹腔注射50ug/kg右美托咪定后进行体外循环手术。选择Morris水迷宫检测三组大鼠空间学习和记忆能力,选择穿梭箱实验检测三组大鼠学习条件反射的能力,选择旷场实验检测三组大鼠在新异环境中的适应能力和认知能力。采用Elisa法测定脑脊液中Aβ、p-Tau及PSD95蛋白含量;采用免疫组化法测定海马及前额叶皮质脑组织中Aβ、p-Tau及PSD95蛋白含量。结果:共有51只大鼠完成本实验全过程,其中实验组23只,右美组28只,对照组30只,三组大鼠实验完成率(分别为76.7%,93.3%和100%)组间差异无统计学意义(P0.05)。1.Morris水迷宫实验:(1)定位航行实验三组大鼠术前逃避潜伏期无明显差异(P0.05),术后第31~35天各组大鼠逃避潜伏期,与实验组相比,对照组与右美组大鼠逃避潜伏期较短(P0.05);与对照组相比,右美组大鼠术后第31、32、34、35天逃避潜伏期较长(P0.05)。(2)空间探索实验与实验组相比,对照组与右美组大鼠穿越原平台次数较多(P0.05);与对照组相比,右美组大鼠穿越原平台次数较少(P0.05)。2.穿梭箱实验与实验组相比,对照组与右美组大鼠主动回避反应次数较多(P0.05),主动及被动回避反应潜伏期较短(P0.05);与对照组相比,右美组大鼠主动回避反应次数较少(P0.01)。3.旷场实验与实验组相比,对照组与右美组大鼠直立次数较多(P0.05),中央格停留时间较短(P0.05);与对照组相比,右美组大鼠中央格停留时间较长(P0.05)。4.脑脊液蛋白含量测试结果与实验组相比,对照组和右美组大鼠脑脊液Aβ及PSD95蛋白含量较高(P0.05),p-Tau蛋白含量较低(P0.05);与对照组相比,右美组大鼠脑脊液Aβ蛋白含量较低(P0.05)。5.脑组织蛋白阳性神经元个数的比较与实验组相比,对照组和右美组大鼠海马及前额叶皮质脑组织Aβ、p-Tau蛋白阳性神经元个数减少,PSD95蛋白阳性神经元个数增加(P0.05);与对照组相比,右美组海马脑组织Aβ蛋白阳性神经元个数增加(P0.05),PSD95蛋白阳性神经元个数减少(P0.05),右美组前额叶皮质脑组织Aβ、p-Tau蛋白阳性神经元个数增加(P0.05),PSD95蛋白阳性神经元个数减少(P0.05)。结论:1老龄大鼠行体外循环手术对术后认知功能的影响在行为学方面表现为:影响空间学习和记忆的形成,导致学习条件反射的能力降低,并减弱其在新异环境中的适应能力和认知能力;而术前使用右美托咪定能使上述症状得到改善。2行体外循环手术的老龄大鼠脑脊液中Aβ及PSD95蛋白含量增高,p-Tau蛋白含量降低;而术前使用右美托咪定能降低脑脊液中蛋白含量改变的幅度。3行体外循环手术的老龄大鼠海马及前额叶皮质脑组织中Aβ、p-Tau蛋白呈低表达,PSD95蛋白呈高表达;而术前使用右美托咪定能降低目标区域脑组织中目标蛋白表达异常的程度。4术前使用右美托咪定能够降低行体外循环手术的老龄大鼠术后认知功能障碍的发生,其机制可能是通过调节Aβ、p-Tau及PSD95蛋白表达来实现的。
[Abstract]:Objective: To investigate the effect and possible mechanism of postoperative cognitive function of the aged rats undergoing cardiopulmonary bypass operation before and after the operation. Methods: 90 healthy male SD rats from 18 to 20 months of age were randomly divided into experimental group, control group and right group. In the right group, the rats were injected with 50ug/ kg dexmetomidine, and the operation was carried out after cardiopulmonary bypass. The spatial learning and memory ability of three groups of rats were tested by the Morris water maze. The ability of three groups of rats to study the conditioned reflex was selected by the experiment of the shuttle box, and the adaptive ability and the cognitive ability of the three groups of rats in the new environment were selected. The content of A-, p-Tau and PSD95 in the cerebrospinal fluid was determined by elisa, and the content of A-, p-Tau and PSD95 in the brain of the hippocampus and prefrontal cortex was determined by immunohistochemistry. Results: The whole process of the experiment was completed in 51 rats, 23 of the experimental group, 28 in the right and 30 in the control group, and the experimental completion rate of the three groups (76.7%, 93.3% and 100%, respectively). (1) There was no significant difference in the avoidance latency of the three groups of rats (P0.05). The latency of the 31, 32, 34 and 35 days after operation in the right group was longer than that in the right group (P0.05). (2) Compared with the experimental group, the number of the rats in the control group and the right group was much higher than that of the control group (P0.05); the number of the rats in the right and the right group was less than that of the control group (P0.05). Compared with the experimental group, the number of active avoidance responses in the control group and the right group (P0.05), the active and passive avoidance response latency was shorter (P <0.05), and the number of active avoidance responses in the right-group rats was less than that of the control group (P0.01). Compared with the experimental group, the vertical number of the rats in the control group and the right group was much higher (P0.05), and the residence time of the central cell was shorter (P <0.05), and the residence time of the central cell in the right-US group was longer than that of the control group (P0.05). Compared with the control group, the content of CSF-A and PSD95 in the spinal fluid of the control group and the right group were higher (P0.05), and the content of the P-Tau protein was lower (P0.05). Compared with the control group, the number of positive neurons in the brain tissue of the rats in the control group and the right group decreased, the number of the positive neurons of the p-Tau protein was decreased, and the number of the positive neurons of the PSD95 protein was increased (P0.05); and compared with the control group, the number of the positive neurons of the brain tissue protein was reduced, and the number of the positive neurons of the PSD95 protein was increased (P0.05). The number of positive neurons in the hippocampus of the right group was increased (P0.05), the number of positive neurons of the PSD95 protein was decreased (P0.05), and the number of positive neurons in the prefrontal cortex of the right group was increased (P0.05), and the number of positive neurons of the PSD95 protein was decreased (P0.05). Conclusion: 1. The effect of cardiopulmonary bypass on the cognitive function of aged rats is shown as follows: the formation of spatial learning and memory, the ability of learning conditioned reflex, and the ability to adapt to the cognitive function in the new environment; The results showed that the content of A-and PSD95 in the cerebrospinal fluid of aged rats with cardiopulmonary bypass (CPB) increased, and the content of p-Tau protein was lower. The changes of protein content in the CSF can be reduced by the use of the right meetomidate before the operation. The expression of A-and p-Tau in the brain of the hippocampus and the prefrontal cortex of the aged rats with cardiopulmonary bypass is low, and the PSD95 protein is highly expressed. It is possible to reduce the level of target protein expression in the brain tissue of the target region by using the right-meetomidate before operation. p-Tau and pSD95 protein expression.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
本文编号：2371245
[Abstract]:Objective: To investigate the effect and possible mechanism of postoperative cognitive function of the aged rats undergoing cardiopulmonary bypass operation before and after the operation. Methods: 90 healthy male SD rats from 18 to 20 months of age were randomly divided into experimental group, control group and right group. In the right group, the rats were injected with 50ug/ kg dexmetomidine, and the operation was carried out after cardiopulmonary bypass. The spatial learning and memory ability of three groups of rats were tested by the Morris water maze. The ability of three groups of rats to study the conditioned reflex was selected by the experiment of the shuttle box, and the adaptive ability and the cognitive ability of the three groups of rats in the new environment were selected. The content of A-, p-Tau and PSD95 in the cerebrospinal fluid was determined by elisa, and the content of A-, p-Tau and PSD95 in the brain of the hippocampus and prefrontal cortex was determined by immunohistochemistry. Results: The whole process of the experiment was completed in 51 rats, 23 of the experimental group, 28 in the right and 30 in the control group, and the experimental completion rate of the three groups (76.7%, 93.3% and 100%, respectively). (1) There was no significant difference in the avoidance latency of the three groups of rats (P0.05). The latency of the 31, 32, 34 and 35 days after operation in the right group was longer than that in the right group (P0.05). (2) Compared with the experimental group, the number of the rats in the control group and the right group was much higher than that of the control group (P0.05); the number of the rats in the right and the right group was less than that of the control group (P0.05). Compared with the experimental group, the number of active avoidance responses in the control group and the right group (P0.05), the active and passive avoidance response latency was shorter (P <0.05), and the number of active avoidance responses in the right-group rats was less than that of the control group (P0.01). Compared with the experimental group, the vertical number of the rats in the control group and the right group was much higher (P0.05), and the residence time of the central cell was shorter (P <0.05), and the residence time of the central cell in the right-US group was longer than that of the control group (P0.05). Compared with the control group, the content of CSF-A and PSD95 in the spinal fluid of the control group and the right group were higher (P0.05), and the content of the P-Tau protein was lower (P0.05). Compared with the control group, the number of positive neurons in the brain tissue of the rats in the control group and the right group decreased, the number of the positive neurons of the p-Tau protein was decreased, and the number of the positive neurons of the PSD95 protein was increased (P0.05); and compared with the control group, the number of the positive neurons of the brain tissue protein was reduced, and the number of the positive neurons of the PSD95 protein was increased (P0.05). The number of positive neurons in the hippocampus of the right group was increased (P0.05), the number of positive neurons of the PSD95 protein was decreased (P0.05), and the number of positive neurons in the prefrontal cortex of the right group was increased (P0.05), and the number of positive neurons of the PSD95 protein was decreased (P0.05). Conclusion: 1. The effect of cardiopulmonary bypass on the cognitive function of aged rats is shown as follows: the formation of spatial learning and memory, the ability of learning conditioned reflex, and the ability to adapt to the cognitive function in the new environment; The results showed that the content of A-and PSD95 in the cerebrospinal fluid of aged rats with cardiopulmonary bypass (CPB) increased, and the content of p-Tau protein was lower. The changes of protein content in the CSF can be reduced by the use of the right meetomidate before the operation. The expression of A-and p-Tau in the brain of the hippocampus and the prefrontal cortex of the aged rats with cardiopulmonary bypass is low, and the PSD95 protein is highly expressed. It is possible to reduce the level of target protein expression in the brain tissue of the target region by using the right-meetomidate before operation. p-Tau and pSD95 protein expression.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
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