王晓芳,刘利宁,刘 欣,惠 晶,张丽辉.吡拉西坦联合黄芪颗粒对老年痴呆大鼠学习能力、认知功能的影响及机制分析[J].现代生物医学进展英文版,2023,(5):840-844. |
吡拉西坦联合黄芪颗粒对老年痴呆大鼠学习能力、认知功能的影响及机制分析 |
Effect of Piracetam Combined with Astragalus Granules on Learning Ability and Cognitive Function of Senile Dementia Rats and Its Mechanism Analysis |
Received:June 28, 2022 Revised:July 24, 2022 |
DOI:10.13241/j.cnki.pmb.2023.05.008 |
中文关键词: 老年痴呆 吡拉西坦 黄芪颗粒 |
英文关键词: Senile dementia Piracetam Astragalus granules |
基金项目:陕西省卫生健康委科研项目(2018C0326) |
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中文摘要: |
摘要 目的:观察吡拉西坦联合黄芪颗粒对老年痴呆大鼠学习能力、认知功能的影响,并探讨其可能机制。方法:采用双侧海马CA1区注射1 μg β-淀粉样蛋白1-40(Aβ1-40)建立老年痴呆大鼠模型。取40只建模成功的SD大鼠随机分为模型组、吡拉西坦组、黄芪颗粒组和联合组,每组10只。另取10只双侧海马CA1区注射1 μL生理盐水和10只未经任何处理的同龄SD大鼠分别作为假手术组和对照组。建模成功7 d后给予吡拉西坦组、黄芪颗粒组、联合组大鼠分别灌胃吡拉西坦溶液、黄芪颗粒溶液、吡拉西坦+黄芪颗粒混合溶液,给予对照组、假手术组、模型组大鼠灌胃等剂量生理盐水,所有大鼠均连续灌胃治疗30 d。采用Morris水迷宫测试评价大鼠学习和认知功能。处死大鼠后采用TUNEL法检测海马组织神经元凋亡情况,采用比色法检测海马组织天冬氨酸蛋白水解酶-3(caspase-3)和caspase-9活性。结果:(1)6组大鼠第1~5 d的逃避潜伏期均呈显著减少趋势,同组不同时间点比较有显著性差异(P<0.05)。模型组大鼠第1~5 d逃避潜伏期均显著长于其余5组,联合组第1 d的逃避潜伏期显著长于对照组和假手术组(P<0.05),但第2~5 d时的逃避潜伏期与对照组和假手术组比较无差异(P>0.05)。(2)对照组、假手术组和联合组大鼠,吡拉西坦和黄芪颗粒组大鼠平台穿越次数比较无差异(P>0.05)。联合组大鼠平台穿越次数显著多于吡拉西坦组和黄芪颗粒组(P<0.05)。(3)吡拉西坦组、黄芪颗粒组和联合组大鼠海马组织神经元细胞凋亡比例均低于模型组,联合组大鼠海马组织神经元细胞凋亡比例低于吡拉西坦组、黄芪颗粒组(P<0.05)。(4)吡拉西坦组、黄芪颗粒组和联合组大鼠海马组织caspase-3和caspase-9活性均低于模型组,联合组大鼠海马组织caspase-3和caspase-9活性均低于吡拉西坦组、黄芪颗粒组(P<0.05)。结论:吡拉西坦联合黄芪颗粒能够有效改善老年痴呆大鼠学习和认知功能,效果优于单药,其机制可能与两药联合更能有效抑制神经元细胞凋亡信号通路,减轻海马组织神经元损伤有关。 |
英文摘要: |
ABSTRACT Objective: To observe the effect of piracetam combined with astragalus granules on learning ability and cognitive function of senile dementia rats, and explore its possible mechanism. Methods: Injected into bilateral hippocampal CA1 area 1 μg β-Amyloid protein 1-40 (Aβ1-40) was used to establish the rat model of senile dementia. Forty SD rats were randomly divided into model group, piracetam group, astragalus granule group and combination group, with 10 rats in each group. Another 10 rats were injected into bilateral hippocampal CA1 area μL Normal saline and 10 SD rats of the same age without any treatment were used as sham operation group and control group respectively. Seven days after successful modeling, rats in piracetam group, astragalus granule group and combination group were given piracetam solution, astragalus granule solution, piracetam+astragalus granule mixed solution by gavage respectively, and rats in control group, sham operation group and model group were given normal saline at the same dose by gavage. All rats were given continuous gavage treatment for 30 days. Morris water maze test was used to evaluate the learning and cognitive functions of rats. After the rats were killed, TUNEL method was used to detect neuronal apoptosis in the hippocampus, and colorimetric method was used to detect the level of serum Ach, the activity of AchE, and the activities of caspase-3 and caspase-9 in the hippocampus. Results: (1) The escape latency of rats in the six groups from the 1st to the 5th day showed a decreasing trend, and there was a difference at different time points in the same group (P<0.05). The escape latency of rats in the model group was longer than that in the other five groups from the first day to the fifth day, and the escape latency of rats in the combined group was longer than that in the control group and the sham operation group (P<0.05), but there was no difference between the escape latency of rats in the model group and the control group and the sham operation group from the second day to the fifth day(P>0.05). (2) There was no difference in the number of platform crossing between the control group, sham operation group and combined group, piracetam group and astragalus granule group (P>0.05). The number of platform crossing in the combined group was higher than that in piracetam group and astragalus granule group (P<0.05). (3) The percentage of neuronal apoptosis in hippocampus of rats in piracetam group, astragalus granule group and combination group was lower than that in model group, and the percentage of neuronal apoptosis in hippocampus of rats in combination group was lower than that in piracetam group and astragalus granule group(P<0.05). (4) The activities of caspase-3 and caspase-9 in hippocampus of rats in piracetam group, astragalus granule group and combination group were lower than those in model group, and the activities of caspase-3 and caspase-9 in hippocampus of rats in combination group were lower than those in piracetam group and astragalus granule group (P<0.05). Conclusion: Piracetam combined with astragalus granules can effectively improve the learning and cognitive function of alzheimer's rats, and the effect is better than that of single drug. the mechanism may be that the combination of the two drugs can more effectively inhibit the neuronal apoptosis signal pathway, and reduce the neuronal damage in hippocampus. |
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