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中国应用生理学杂志 ›› 2019, Vol. 35 ›› Issue (4): 308-311.doi: 10.12047/j.cjap.5792.2019.065

• 研究论文 • 上一篇    下一篇

鞘氨醇激酶1和1-磷酸鞘氨醇受体2在癫痫大鼠海马组织中表达的变化*

董媛媛1, 王琳2, 褚旭2, 崔帅3, 孔庆霞2△   

  1. 1. 山东大学 齐鲁医学院, 济南 250012;
    2. 济宁医学院附属医院神经内科, 济宁 272000;
    3. 潍坊医学院, 潍坊 261053
  • 收稿日期:2018-12-07 出版日期:2019-07-28 发布日期:2019-11-06
  • 通讯作者: ,Tel: 0537-2903961; E-mail: 438274162@qq.com
  • 基金资助:
    *国家自然科学基金(81371423);山东省医药卫生科技发展计划项目(2018WS450);济宁医学院教师科研基金项目(JYFC2018FKJ109)

Altered expressions of SphK1 and S1PR2 in hippocampus of epileptic rats

DONG Yuan-yuan1, WANG Lin2, CHU Xu2, CUI Shuai3, KONG Qing-xia2△   

  1. 1. Cheeloo College of Medicine, Shandong University, Jinan 250012;
    2. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000;
    3.Weifang Medical University, Weifang 261053, China
  • Received:2018-12-07 Online:2019-07-28 Published:2019-11-06

摘要: 目的:检测鞘氨醇激酶1 (SphK1)和1-磷酸鞘氨醇受体2 (S1PR2) 在癫痫大鼠海马中的表达,探讨SphK1和S1PR2在癫痫中的作用机制。方法:成年雄性SD大鼠108只,随机分为对照(Control)组(n=48)和癫痫(PILO)组(n=60)。癫痫组腹腔注射氯化锂(127 mg/kg),18~20 h后注射匹罗卡品,首剂量为30 mg/kg,发作<IV级的大鼠重复注射匹罗卡品(10 mg/kg);对照组给予等剂量的生理盐水代替匹罗卡品。根据造模后观察时间和行为学改变,随机分为3个大组,6个亚组:急性期组(E6 h、E1 d、E3 d)、潜伏期组(E7 d)和慢性期组(E30 d、E56 d),每个亚组中对照大鼠和癫痫大鼠各8只。每组取4只大鼠麻醉取海马,另4只取大脑组织。运用Western blot检测SphK1、S1PR2在大鼠海马组织中的表达变化,免疫荧光检测星形胶质细胞活化增生情况及SphK1、S1PR2在星形胶质细胞中的定位表达。结果:与Control组比较,SphK1在造模后急性期(E3 d)、潜伏期(E7 d)和慢性期(E30 d、E56 d)海马中的表达均明显升高(P<0.05或P<0.01);S1PR2在急性期(E3 d)、潜伏期(E7 d)和慢性期(E30 d、E56 d)海马组织中的表达均明显下降(P<0.05或P<0.01);癫痫大鼠(E7 d)海马星形胶质细胞活化、增生明显(P<0.05),SphK1和S1PR2在E7d的表达到位为海马星形胶质细胞中。结论:SphK1和S1PR2可能通过调控海马星形胶质细胞活化增生和影响神经元兴奋性参与了癫痫的发病。

关键词: 癫痫, 大鼠, 鞘氨醇激酶1, 1-磷酸鞘氨醇受体2, 星形胶质细胞

Abstract: Objective: To observe the expressions of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 2 (S1PR2) in hippocampus of epileptic rats and to investigate the pathogenesis of SphK1 and S1PR2 in epilepsy. Methods: One hundred and eight male Sprague-Dawley (SD) rats were randomly divided into control group (n=48) and pilocarpine (PILO) group (n=60). A robust convulsive status epilepticus (SE) was induced in PILO group rats by the application of pilocarpine. Control group rats were injected with respective of physiological saline. Pilocarpine group was randomly divided into 6 subgroups (n=8): acute group (E6 h, E1 d, E3 d), latent group (E7 d) and chronic group (E30 d, E56 d). Each subgroup has 8 control rats and 8 epileptic rats. Hippocampal tissue and brain slices were obtained from control rats and rats subjected to the Li-PILO model of epilepsy at 6 h, 1 d, 3 d,7 d,30 d and 56 d after status epilepticus (SE). Western blot technique was used to determine the expressions of SphK1 and S1PR2 in hippocampus at different point of time after pilocarpine treatment. Immunofluorescence was applied to detect the activation and proliferation of hippocampal astrocytes and the localization of SphK1 and S1PR2 in rat hippocampal astrocytes. Results: Compared with control group, the levels of SphK1 in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d) were significantly increased while the expressions of S1PR2 were decreased in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d)(P<0.05 or P<0.01). Immunofluorescence results showed astrocyte activation and proliferation in hippocampus of epileptic (E7 d) rats (P<0.05). Confocal microscopy confirmed the preferential expressions of SphK1 and S1PR2 in epileptic rat(E7 d)hippocampal astrocytes. Conclusion: The results indicate that SphK1 and S1PR2 may play an important role in the pathogenesis of epilepsy by regulating the activation and proliferation of hippocampal astrocytes and altering neuronal excitability.

Key words: epilepsy, rat, sphingosine kinase 1, sphingosine-1-phosphate receptor 2, astrocyte

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