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目的:考察骆驼蓬总碱对血管性痴呆(VD)大鼠学习记忆的影响及作用机制。方法:采用双侧颈总动脉结扎制作血管性痴呆模型,造模后第30d将大鼠分成模型组、骆驼蓬总碱25mg/kg、12.5mg/kg、6.25mg/kg组,尼麦角林片7mg/kg组和假手术组,连续给药30d。Morris水迷宫检测学习记忆,免疫组织化学法检测海马CA1区突触素(synaptophysin,syn)微管相关蛋白2(microtubule-associated protein 2,MAP-2)蛋白表达,硝酸还原酶法测定一氧化氮(NO)含量,化学比色法测定一氧化氮合酶(NOS)活性。结果:与模型组相比,骆驼蓬总碱25mg/kg第3、4d潜伏期明显缩短,12.5mg/kg组第4d潜伏期明显缩短。骆驼蓬总碱25mg/kg、12.5mg/kg剂量组站台穿越次数明显增加。骆驼蓬总碱25mg/kg、12.5mg/kg剂量组海马区syn、MAP-2的积分光密度值增加。骆驼蓬总碱25mg/kg海马NO含量、NOS活性降低。结论:骆驼蓬总碱能够改善VD大鼠的学习记忆能力,其机制可能与上调海马syn、MAP-2蛋白表达,提高突触可塑性,降低NO含量,抑制NOS活性有关。
Objective: To investigate the effect of Peganum harmala on learning and memory of vascular dementia (VD) rats and its mechanism. Methods: The model of vascular dementia was established by ligation of bilateral common carotid arteries, and the rats were divided into model group, Peganum alkaloids 25mg / kg, 12.5mg / kg, 6.25mg / kg, 7mg / kg group and sham operation group, continuous administration 30d. Morris water maze was used to detect learning and memory, protein expression of synaptophysin (syn) microtubule-associated protein 2 (MAP-2) in hippocampal CA1 area was detected by immunohistochemical method, nitric oxide (NO) content, nitric oxide synthase (NOS) activity was determined by chemical colorimetry. Results: Compared with the model group, the incubation period of Peganum harmala total alkaloids at 25 mg / kg was significantly shortened at 3 and 4 days, and the incubation period at 4 and 12 days in 12.5 mg / kg group was significantly shortened. Peganum alkaloids 25mg / kg, 12.5mg / kg dose group significantly increased the number of platform traverses. The integral optical density of syn-MAP-2 in the hippocampus increased with the total alkaloids of Peganum harmala 25 mg / kg and 12.5 mg / kg. Peganum alkaloids 25mg / kg NO content in the hippocampus, NOS activity decreased. Conclusion: Alkaloids from Peganum harmala improve the learning and memory abilities of VD rats. The mechanism may be related to the up-regulation of syn-MAP-2 protein expression, synaptic plasticity, NO reduction and NOS activity in hippocampus.