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祁敏芳,吴慧娟,童军卫,蒋永泼,钱玲珠,杨卫星,徐挺立.丹参素经PI3K/AKT信号通路改善血管性痴呆小鼠认知功能的机制研究[J].浙江中西医结合杂志,2021,31(4):
丹参素经PI3K/AKT信号通路改善血管性痴呆小鼠认知功能的机制研究
The mechanism of Danshensu improving the cognitive function of vascular dementia mice through PI3K/AKT signal pathway
投稿时间:2020-09-23  修订日期:2021-03-18
DOI:
中文关键词:  丹参素  PI3K/AKT信号通路  认知功能  血管性痴呆
英文关键词:Danshensu  PI3K/AKT signaling pathway  Cognitive function  Vascular dementia
基金项目:台州市科技计划项目(编号:1902ky70)
作者单位E-mail
祁敏芳 台州恩泽医疗中心集团路桥医院重症医学科 minfangqi8347@163.com 
吴慧娟 台州恩泽医疗中心集团路桥医院重症医学科  
童军卫 台州恩泽医疗中心集团恩泽医院脑外科  
蒋永泼   
钱玲珠   
杨卫星   
徐挺立 台州恩泽医疗中心集团路桥医院重症医学科  
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中文摘要:
      目的:基于磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路探讨丹参素对血管性痴呆小鼠认知功能的改善情况。方法:将60只昆明种小鼠按随机数字表法分为6组:正常对照组、模型组、阳性对照组(尼莫地平注射液,2 mg·kg-1)、丹参素低(10 mg·kg -1)、中(20 mg·kg -1)、高(30 mg·kg -1)剂量组,每组10只。模型组、阳性对照组、丹参素低、中、高剂量组小鼠构建血管性痴呆模型。建模成功后,从第1天开始丹参素各剂量组和阳性对照组腹腔注射相应的药物,正常对照组和模型组腹腔注射等量生理盐水,每天1次,持续28d。给药结束后对小鼠进行水迷宫实验,检测小鼠脑损伤相关因子血清星形胶质源性蛋白(S-100β)、神经元特异性烯醇化酶(NSE)含量,苏木精-伊红(HE)染色观察小鼠脑组织结构,蛋白免疫印迹(Western blot)法检测小鼠脑组织中PI3K、AKT蛋白水平。结果:正常对照组小鼠脑组织结构正常,细胞排列整齐,无明显空泡结构;模型组可见明显的脑白质受损,细胞排列紊乱,视野中大量空泡结构;在给予丹参素干预后,随着丹参素给药剂量的增加,可见脑组织细胞排列逐渐变整齐,空泡结构逐渐减少。与正常对照组比较,模型组小鼠逃避潜伏期、血清S-100β、NSE含量显著升高,脑组织中PI3K、AKT蛋白表达水平显著降低(P<0.05);与模型组比较,丹参素低、中、高剂量组和阳性对照组小鼠逃避潜伏期、血清S-100β、NSE含量显著降低,脑组织中PI3K、AKT蛋白表达水平显著升高(P<0.05);随着丹参素给药剂量的增加,小鼠逃避潜伏期、血清S-100β、NSE含量逐渐降低,脑组织中PI3K、AKT蛋白表达水平逐渐升高,具有量-效关系(P<0.05);丹参素高剂量组和阳性对照组上述指标差异无统计学意义(P>0.05)。结论:丹参素可通过调节PI3K/AKT信号通路及相关细胞因子,改善血管性痴呆小鼠的认知功能障碍。
英文摘要:
      Objective: To investigate the mechanism of Danshensu improving the cognitive function of vascular dementia mice through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) signal pathway. Methods: Sixty Kunming mice were randomly divided into six groups: normal control group, model group, positive control group (nimodipine injection, 2 mg.kg-1), Danshensu low (10 mg.kg-1), medium (20 mg.kg-1), high (30 mg.kg-1) dose group with 10 mice in each group. The mice in the model group, positive control group, low, medium and high dose Danshensu group were used to construct vascular dementia model. After the model was established successfully, the corresponding drugs were injected intraperitoneally in each dose Danshensu group and positive control group from the first day, and equal volume of normal saline was injected intraperitoneally in the normal control group and model group for once a day for 28 days. At the end of administration, water maze test was carried out in mice, the brain injury related factors serum astrocyte derived protein (S-100β) and neuron specific enolase (NSE) were detected were detected, hematoxylin eosin(HE) staining was used to observe the brain tissue structure of mice, and Western blot was used to detect the levels of PI3K and AKT protein in the brain tissue of mice. Results: In the normal control group, the brain tissue structure was normal, the cells were arranged orderly, and there was no obvious vacuole structure; in the model group, the white matter was obviously damaged, the cell arrangement was disordered, and a large number of vacuoles were found in the visual field; after the administration of Danshensu, with the increase of the dosage of Danshensu, the arrangement of brain tissue cells gradually became regular, and the vacuole structure gradually decreased. Compared with the normal control group, the escape latency, serum S-100β and NSE contents of the model group were increased (P<0.05), and the expression level of PI3K and Akt protein in brain tissue decreased significantly (P<0.05). Compared with the model group, the escape latency, serum S-100β and NSE contents in the low, medium and high dose Danshensu groups and the positive control group were significantly decreased, and the expression levels of PI3K and Akt protein in brain tissue were significantly increased (P<0.05). With the increase of Danshensu dosage, escape latency, serum S-100β and NSE contents were gradually decreased, and the expression levels of PI3K and Akt protein in brain tissue were gradually increased, with a dose-response relationship (P<0.05). There was no significant difference between Danshensu high dose group and positive control group (P>0.05). Conclusion: Danshensu can improve the cognitive dysfunction of vascular dementia mice by regulating PI3K/AKT signal pathway and related cytokines.
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