| 孙克德,李 娜,唐 彦,闫 欣,马京京,武 娇,张晓红,杜双霞.丁苯酞对缺血性脑卒中大鼠记忆能力及海马5-HT1A受体和PKA信号通路活化的影响[J].,2021,(4):639-644 |
| 丁苯酞对缺血性脑卒中大鼠记忆能力及海马5-HT1A受体和PKA信号通路活化的影响 |
| Effects of Butylphthalide on Memory Ability and Activation of 5-HT1A Receptor and PKA Signaling Pathway in Hippocampus of Rats with Ischemic Stroke |
| 投稿时间：2020-04-28 修订日期：2020-05-23 |
| DOI：10.13241/j.cnki.pmb.2021.04.008 |
| 中文关键词: 缺血性脑卒中 丁苯酞 学习和记忆能力 5-HT1A受体 PKA信号通路 |
| 英文关键词: Ischemic stroke Butylphthalide Learning and memory ability 5-HT1A receptor PKA signaling pathway |
| 基金项目:河北省保定市科技支撑计划项目(17ZF222) |
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| 中文摘要: |
| 摘要 目的：研究丁苯酞对缺血性脑卒中大鼠学习和记忆能力的影响和大鼠海马5-HT1A受体和PKA信号通路的调控作用。方法：将雄性SD大鼠随机分为假手术组、模型组和丁苯酞组（n=15）。丁苯酞组大鼠建立大脑中动脉闭塞模型，并按照每天60 mg/kg的剂量灌胃丁苯酞，假手术组和模型组灌胃等体积的玉米油，共给药2周。治疗完成后对各组大鼠进行神经功能缺损评估和Morris水迷宫测试（n=15）。通过磁共振成像（MRI）检测梗塞区域（n=15）。ELISA法检测海马组织PKA激酶活性（n=6）。使用钙检测试剂盒测定海马组织的细胞内[Ca2+]浓度（n=6）。Western blot检测海马组织中5-羟色胺（1A）受体（5-HT1A）、谷氨酸N-甲基-D-天冬氨酸受体1(NMDA1)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体1(AMPA1)的表达（n=6）。结果：与模型组相比：丁苯酞组大鼠的逃避潜伏期显著降低，而穿越平台次数显著升高（P<0.05）；大鼠的神经功能缺损评分和脑梗死体积较显著降低（P<0.05）；大鼠的PKA激酶活性和细胞内[Ca2+]浓度显著升高（P<0.05）；丁苯酞组大鼠的5-HT1A蛋白相对表达量显著降低，而AMPA1和NMDA1的磷酸化水平显著升高（P<0.05）。结论：丁苯酞可改善缺血性脑卒中大鼠的学习和记忆能力，下调海马5-HT1A受体活性并激活PKA信号通路。 |
| 英文摘要: |
| ABSTRACT Objective: The aim of this study was to reveal the effect of butylphthalide on learning and memory ability of rats with ischemic stroke, and the regulation of butylphthalide on 5-HT1A receptor and PKA signaling pathway in hippocampus of rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into a sham group, a model group and a butylphthalide group (n=15). A model of middle cerebral artery occlusion was established in rats in the butylphthalide group, and the rats were administrated orally with butylphthalide at a dose of 60 mg / kg per day for 2 weeks. The sham group and the model group were administered orally with equal volume of corn oil for 2 weeks. After the treatment, neurological deficit assessment and Morris water maze test were performed on each group of rats (n=15). The infarcted area was detected by magnetic resonance imaging (MRI) (n=15). ELISA was performed to determine PKA kinase activity in hippocampus (n=6). Intracellular [Ca2+] concentration in the hippocampus was measured using a calcium detection kit (n=6). Western blot was used to detect the expression of serotonin (1A) receptor (5-HT1A), N-methyl-D-aspartate receptor 1 (NMDA1) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPA1) in hippocampus (n=6). Results: Compared with the model group: the escape latency of rats in the butylphthalide group were significantly reduced, but the number of crossing platforms was greatly increased (P<0.05); the neurologic deficit score and cerebral infarction volume of rats were tremendously reduced (P<0.05); the PKA kinase activity and intracellular [Ca2+] concentration in rats increased dramatically (P<0.05); the relative expression of 5-HT1A protein decreased markedly in rats in the phthalein group, while the phosphorylation level of AMPA1 and NMDA1 increased sharply (P<0.05). Conclusion: Butylphthalide can improve the learning and memory ability of rats with ischemic stroke, and down-regulate the activity of 5-HT1A receptor, and activate the PKA signaling pathway in hippocampus. |
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