不同程度控制性降压对大鼠海马CA1区Aβ蛋白及tau蛋白磷酸化表达的影响
发布时间：2018-08-14 16:02
【摘要】：目的:通过硝普钠联合艾司洛尔对大鼠进行不同程度的控制性降压,观察其对大鼠术后认知功能的影响,并观察其对大鼠海马CA1区Aβ蛋白及tau蛋白磷酸化表达的影响。方法:本实验包括两部分内容:(1)不同程度控制性降压对大鼠术后认知功能的影响。(2)不同程度控制性降压对大鼠海马CA1区Aβ蛋白及tau蛋白磷酸化表达的影响。选择健康成年雄性SD大鼠96只,体重280~320g,采用随机数字表法,将大鼠随机分为4组,每组24只。正常对照组(C组):不做任何处理;控制性降压Ⅰ组(CH1组):联合应用硝普钠和艾司洛尔使MAP降压基础值的30%;控制性降压Ⅱ组(CH2组):联合应用硝普钠和艾司洛尔使MAP降压基础值的45%;控制性降压Ⅲ组(CH3组):联合应用硝普钠和艾司洛尔使MAP降压基础值的60%;并维持目标血压1h,所有大鼠降压1h后均复压,复压时间为2h。术中严密监测各组大鼠的各项血流动力学指标,并进行动脉血气分析,分别于术前及术后对各组大鼠进行Morris水迷宫实验测定认知功能,于水迷宫测试结束后处死大鼠,取大鼠海马组织,进行HE染色,光镜下观察大鼠海马组织CA1区神经元病理学结果,TUNEL法测定海马神经元凋亡情况,并采用Western blot法检测海马Aβ蛋白和磷酸化tau蛋白表达情况。结果:(1)与C组比较,CH2及CH3组大鼠术后逃避潜伏期均延长,穿越平台次数均减少(P0.05),CH1组比较差异无统计学意义(P0.05);与CH1组比较,CH2及CH3组大鼠术后逃避潜伏期均延长,穿越平台次数均减少(P0.05);与CH2组比较,CH3组大鼠术后逃避潜伏期延长,穿越平台次数减少(P0.05);(2)HE染色:C组及CH1组大鼠海马CA1区神经元形态和结构未见异常;CH2组海马CA1区神经元排列不规则,胞体缩小,细胞间隙欠清楚,神经元数量轻度减少;CH3组CA1区神经元细胞排列紊乱,出现大量凋亡细胞。(3)与C组比较,CH2及CH3组大鼠术后海马Aβ蛋白和磷酸化tau蛋白表达均升高(P0.05),CH1组比较差异无统计学意义(P0.05);与CH1组比较,CH2及CH3组大鼠术后海马Aβ蛋白和磷酸化tau蛋白表达均升高(P0.05);与CH2组比较,CH3组大鼠术后海马Aβ蛋白和磷酸化tau蛋白表达升高(P0.05)。结论:1、控制性降压达一定程度后可导致大鼠术后认知功能障碍,并随着降压幅度的增加,术后认知功能障碍加重。2、控制性降压导致大鼠术后认知功能障碍的机制可能与其上调海马CA1区Aβ蛋白及磷酸化tau蛋白表达有关。
[Abstract]:Aim: to observe the effect of sodium nitroprusside combined with esmolol on postoperative cognitive function and phosphorylation of A 尾 protein and tau protein in CA1 region of rat hippocampus. Methods: this experiment includes two parts: (1) the effect of controlled hypotension on the cognitive function of rats after operation, (2) the effect of controlled hypotension on the expression of A 尾 protein and tau protein phosphorylation in CA1 region of rat hippocampus. 96 healthy adult male SD rats weighing 280 ~ 320g were randomly divided into 4 groups with 24 rats in each group. Normal control group (group C): no treatment; Controlled hypotension group I (CH1 group): combined use of sodium nitroprusside and esmolol to reduce MAP blood pressure base value 30; controlled hypotension group II (CH2 group): combined use of sodium nitroprusside and esmolol to make MAP base value 45; controlled hypotension group III (CH3) Group A: combined use of sodium nitroprusside and esmolol to reduce blood pressure by 60% of the baseline value of MAP and maintain the target blood pressure for 1 hour, and all rats were repressed after 1 hour of hypotension. The repressing time is 2 h. The hemodynamic indexes of each group were closely monitored during the operation, and arterial blood gas analysis was performed. The cognitive function of each group was measured by Morris water maze test before and after operation, and the rats were killed after the water maze test. The hippocampal tissues of rats were stained with HE, and the neuronal apoptosis in the CA1 area of hippocampus was observed by light microscopy. The expression of A 尾 protein and phosphorylated tau protein in hippocampus was detected by Western blot method, Tunel method was used to detect the apoptosis of hippocampal neurons. Results: (1) compared with group C and group C, the escape latency of rats in CH2 and CH3 groups were prolonged and the times of crossing platform were decreased (P0.05), there was no significant difference between CH1 group and group C (P0.05), and the escape latency of CH2 group and CH3 group were prolonged compared with that of group C (P0.05). Compared with CH2 group, the escape latency of CH3 group was longer than that of CH2 group. The number of crossing platform decreased (P0.05); (2) in group C and CH1, there was no abnormality in the morphology and structure of hippocampal CA1 neurons. In CH2 group, the hippocampal CA1 neurons arranged irregularly, the cell bodies were reduced, and the gap between neurons was not clear. The number of neurons decreased slightly in CH3 group, and the neuronal cells in the CA1 region of CH3 group were disordered. A large number of apoptotic cells appeared. (3) compared with group C and CH3 group, the expression of A 尾 protein and phosphorylated tau protein in hippocampus of rats in CH2 and CH3 groups increased significantly (P0.05), and there was no significant difference between CH1 group and CH1 group (P0.05), and the expression of A 尾 protein in hippocampus of CH2 and CH3 groups was higher than that of CH1 group (P0.05). Compared with CH2 group, the expression of hippocampal A 尾 protein and phosphorylated tau protein increased in CH3 group (P0.05). ConclusionThe controlled hypotension to a certain extent may lead to postoperative cognitive dysfunction in rats, and with the increase of the amplitude of hypotension, The mechanism of cognitive dysfunction induced by controlled hypotension may be related to the up-regulation of expression of A 尾 protein and phosphorylated tau protein in hippocampal CA1.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
本文编号：2183387
[Abstract]:Aim: to observe the effect of sodium nitroprusside combined with esmolol on postoperative cognitive function and phosphorylation of A 尾 protein and tau protein in CA1 region of rat hippocampus. Methods: this experiment includes two parts: (1) the effect of controlled hypotension on the cognitive function of rats after operation, (2) the effect of controlled hypotension on the expression of A 尾 protein and tau protein phosphorylation in CA1 region of rat hippocampus. 96 healthy adult male SD rats weighing 280 ~ 320g were randomly divided into 4 groups with 24 rats in each group. Normal control group (group C): no treatment; Controlled hypotension group I (CH1 group): combined use of sodium nitroprusside and esmolol to reduce MAP blood pressure base value 30; controlled hypotension group II (CH2 group): combined use of sodium nitroprusside and esmolol to make MAP base value 45; controlled hypotension group III (CH3) Group A: combined use of sodium nitroprusside and esmolol to reduce blood pressure by 60% of the baseline value of MAP and maintain the target blood pressure for 1 hour, and all rats were repressed after 1 hour of hypotension. The repressing time is 2 h. The hemodynamic indexes of each group were closely monitored during the operation, and arterial blood gas analysis was performed. The cognitive function of each group was measured by Morris water maze test before and after operation, and the rats were killed after the water maze test. The hippocampal tissues of rats were stained with HE, and the neuronal apoptosis in the CA1 area of hippocampus was observed by light microscopy. The expression of A 尾 protein and phosphorylated tau protein in hippocampus was detected by Western blot method, Tunel method was used to detect the apoptosis of hippocampal neurons. Results: (1) compared with group C and group C, the escape latency of rats in CH2 and CH3 groups were prolonged and the times of crossing platform were decreased (P0.05), there was no significant difference between CH1 group and group C (P0.05), and the escape latency of CH2 group and CH3 group were prolonged compared with that of group C (P0.05). Compared with CH2 group, the escape latency of CH3 group was longer than that of CH2 group. The number of crossing platform decreased (P0.05); (2) in group C and CH1, there was no abnormality in the morphology and structure of hippocampal CA1 neurons. In CH2 group, the hippocampal CA1 neurons arranged irregularly, the cell bodies were reduced, and the gap between neurons was not clear. The number of neurons decreased slightly in CH3 group, and the neuronal cells in the CA1 region of CH3 group were disordered. A large number of apoptotic cells appeared. (3) compared with group C and CH3 group, the expression of A 尾 protein and phosphorylated tau protein in hippocampus of rats in CH2 and CH3 groups increased significantly (P0.05), and there was no significant difference between CH1 group and CH1 group (P0.05), and the expression of A 尾 protein in hippocampus of CH2 and CH3 groups was higher than that of CH1 group (P0.05). Compared with CH2 group, the expression of hippocampal A 尾 protein and phosphorylated tau protein increased in CH3 group (P0.05). ConclusionThe controlled hypotension to a certain extent may lead to postoperative cognitive dysfunction in rats, and with the increase of the amplitude of hypotension, The mechanism of cognitive dysfunction induced by controlled hypotension may be related to the up-regulation of expression of A 尾 protein and phosphorylated tau protein in hippocampal CA1.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
【参考文献】
相关期刊论文 前1条
1 李静;周华东;王延江;张猛;许志强;方传勤;;脑缺血对阿尔茨海默病模型大鼠认知功能的影响及其机制探讨[J];中国神经免疫学和神经病学杂志;2008年05期
，本文编号：2183387
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