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目的研究不同时间给予普萘洛尔对条件性恐惧大鼠恐惧记忆保持及海马CA3区神经元形态的影响。方法成年雄性SD大鼠24只,采用声音结合强烈足底电击建立大鼠条件性恐惧模型。大鼠建模成功后分为对照组(不给药,只在相应时间点进行恐惧水平测验)、立即给药组(15 min内给予普萘洛尔)和24 h后给药组(24 h后给予普萘洛尔),每组8只。给药组在建模后前3 d每天恐惧测试前给予普萘洛尔后再检测各组大鼠条件性恐惧记忆水平,于第20天完成恐惧记忆测试后处死大鼠,用高尔基染色法检测大鼠海马神经元形态和数量,电镜观察海马超微结构的变化。结果①条件性恐惧建模后,第1天3组大鼠恐惧水平差异无统计学意义(P>0.05);第2、3、20天时,两给药组大鼠恐惧水平逐渐降低,且3组大鼠在同一时间点恐惧水平差异有统计学意义(P<0.05,P<0.01),立即给药组恐惧水平最低,对照组恐惧水平最高。建模后第20天,对照组大鼠恐惧水平仍然较高。②建模后第20天,两给药组海马神经元CA3区锥体细胞数量[立即给药组(4.94±2.67)个,24 h后给药组(4.65±1.98)个]均大于对照组[(3.58±2.03)个],其中立即给药组明显大于对照组(P<0.05)。③电镜显示对照组海马CA3区超微结构出现异常改变,而两给药组超微结构变化不明显。结论条件性恐惧水平与海马结构发生的形态学异常变化有关,而早期应用β受体阻断剂普萘洛尔阻断β受体抑制去甲肾上腺能神经系统活性,可以在一定程度上降低条件性恐惧、减轻海马神经元结构功能损害。
Objective To investigate the effects of propranolol on fear memory retention and neuronal morphology in hippocampal CA3 area of rats with conditioned fear at different times. Methods Twenty - four adult male Sprague - Dawley rats were used to establish a conditioned stress model of rats by sound combined with intense foot shock. After successful modeling, rats were divided into control group (no administration, only fear level test at the corresponding time points), immediate administration group (propranolol within 15 min) and administration group 24 h After giving propranolol), 8 in each group. The rats in the drug-treated group were given propranolol before the fear test for the first 3 days before modeling, and then the conditioned fear memory of the rats in each group was tested. After the fear memory test was completed on the 20th day, the rats were killed and the rats were killed by the Galerkin staining Morphology and number of hippocampal neurons in rats were observed by electron microscopy and their ultrastructural changes were observed. Results ① After fear conditioning, there was no significant difference in fear level between the three groups on the first day (P> 0.05). On the 2nd, 3rd and 20th day, the fear level decreased gradually in the two groups The level of fear in the rats at the same time point had significant difference (P <0.05, P <0.01), the fear level in the immediate medication group was the lowest, and the fear level in the control group was the highest. On the 20th day after modeling, the fear level of the control rats was still high. ②The number of pyramidal neurons in hippocampal CA3 area of the two administration groups after treatment (4.94 ± 2.67 for immediate treatment and 4.65 ± 1.98 for 24 h) were higher than those in control group [(3.58 ± 2.03)], which was significantly higher in the immediate administration group than in the control group (P <0.05). ③ Electron microscopy showed abnormal changes in the ultrastructure of hippocampal CA3 region in the control group, while the ultrastructural changes in the two administration groups were not obvious. Conclusions Conditional fear level is related to the abnormal morphological changes of hippocampal formation. However, the early application of beta-blocker propranolol to block beta-receptor inhibits the activity of noradrenergic nervous system may reduce the condition to some extent Fear of nature, reduce structural damage of hippocampal neurons.