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目的观察肾上腺素能受体拮抗剂普萘洛尔和哌唑嗪对慢性轻度不可预知应激模型(CUMS)大鼠行为学及急应激暴露后血清皮质酮水平(CORT)、中枢海马诱导型一氧化氮合酶(iNOS)表达的影响,探讨其应激保护作用。方法健康成年Wistar雄性大鼠32只,随机分为4组:空白对照组、CUMS组、普萘洛尔组和哌唑嗪组。CUMS造模前后,用旷场实验测各组大鼠的行为学变化。造模结束后,应激动物接受1.0 mA,5 s,持续60次的急性电击刺激,2 h后断头处死。放射免疫分析法测大鼠血清皮质醇含量换算成皮质酮含量;Western blot测中枢海马中iNOS表达量。结果与对照组比较,普萘洛尔组大鼠水平运动得分、竖立次数和修饰次数减少(P<0.05),中枢海马iNOS表达量明显增加(P<0.01);哌唑嗪组大鼠与对照组比较无明显差异,血清CORT水平明显高于普萘洛尔组(P<0.05)。结论哌唑嗪可明显改善CUMS模型大鼠的行为学改变,有利于应激个体再次遭遇急性应激时CORT的调动,减轻应激导致中枢海马损伤的程度。普萘洛尔可缓解应激时的焦虑水平,但不能扭转应激对中枢海马的损伤。
Objective To investigate the effects of propranolol and prazosin on the behavior and the levels of serum corticosterone (CORT) and the central hippocampal induction in chronic mild unpredictable stress model (CUMS) rats. Type nitric oxide synthase (iNOS) expression, explore its stress protective effect. Methods Thirty-two adult Wistar male rats were randomly divided into 4 groups: blank control group, CUMS group, propranolol group and prazosin group. Before and after CUMS modeling, the open field test was used to measure the behavioral changes of rats in each group. After the modeling, the stress animals received 1.0 mA for 5 seconds and sustained 60 times of acute electric shocks, and were killed after 2 hours. Serum cortisol content was measured by radioimmunoassay (RIA) in terms of corticosterone content; iNOS expression in central hippocampus was measured by Western blot. Results Compared with the control group, the level of iNOS expression in the central hippocampus was significantly increased in the propranolol group (P <0.01), and decreased in the propranolol group (P <0.05) There was no significant difference between groups. Serum CORT level was significantly higher than that of propranolol group (P <0.05). Conclusion Prazosin can significantly improve the behavioral changes in rats with CUMS, which is conducive to the mobilization of CORT in stress-induced acute stress and reduce the degree of stress-induced central hippocampal damage. Propranolol relieved stress levels but did not reverse the stress-induced damage to the central hippocampus.