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山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (2): 17-21.

• 基础医学 • 上一篇    下一篇

Ang Ⅱ诱导大鼠原代海马神经细胞衰老的作用及机制

张娜娜1,王立祥1,曾季平2,魏欣冰1,曹敏敏1,刘慧青1,孙霞1,张岫美1   

  1. 山东大学医学院  1. 药理学研究所; 2. 生物化学与分子生物学研究所, 济南 250012
  • 收稿日期:2012-11-13 出版日期:2013-02-10 发布日期:2013-02-10
  • 通讯作者: 张岫美(1951- ),男,教授,博士生导师,主要从事脑血管药理学研究。E-mail:zhangxm@sdu.edu.cn
  • 作者简介:张娜娜(1986- ),女,硕士研究生,主要从事脑血管药理学研究。E-mail:zhangnana416@126.com
  • 基金资助:

    国家自然科学基金(81172354,81001098);山东省自然科学基金(2009ZRB019RG,ZR2010HZ003)

Role of angiotensin Ⅱ inducing cell senescence in rat hippocampal neurons in primary culture

ZHANG Na-na1, WANG Li-xiang1, ZENG Ji-ping2, WEI Xin-bing1, CAO Min-min1, LIU Hui-qing1, SUN Xia1, ZHANG Xiu-mei1   

  1. 1. Department of Pharmacology; 2. Department of Biochemistry and Molecular Biology,  School of Medicine,
     Shandong University, Jinan 250012, China
  • Received:2012-11-13 Online:2013-02-10 Published:2013-02-10

摘要:

目的   探讨血管紧张素Ⅱ(Ang Ⅱ)诱导大鼠原代海马神经细胞衰老的作用及相关机制。方法   从新生24h内的乳鼠取材,培养大鼠原代海马神经细胞。采用不同浓度诱导剂Ang Ⅱ和不同诱导时间两种方法处理神经细胞,通过衰老相关β-半乳糖苷酶(SA-β-gal)染色法检测神经细胞衰老情况,确定Ang Ⅱ诱导神经细胞衰老的最佳浓度和时间。进一步采用SA-β-gal染色法检测AT1受体阻断剂厄贝沙坦和AT2受体阻断剂PD123319对Ang Ⅱ诱导神经细胞衰老的影响,同时利用Western blot法检测细胞周期调控相关蛋白P53、P21的表达变化,探讨Ang Ⅱ诱导神经细胞衰老的相关机制。结果   10μmol/L Ang Ⅱ作用48h可诱导大鼠原代海马神经细胞衰老,细胞内P53、P21等蛋白表达增加。厄贝沙坦可抑制Ang Ⅱ所致神经细胞衰老,降低P53、P21等蛋白表达,而PD123319对此无作用。结论   Ang Ⅱ可诱导大鼠原代海马神经细胞衰老,此作用由AT1受体介导,其机制可能与P53、P21表达增加有关。

关键词: 血管紧张素Ⅱ;海马;神经细胞;细胞衰老;厄贝沙坦;PD123319

Abstract:

Objective   To investigate the effect and related mechanism of angiotensin Ⅱ (Ang Ⅱ) inducing cell senescence in rat hippocampal neurons in primary culture. Methods   Primary neonatal rat hippocampal neurons were cultured. Senescence-associated β-galactosidase (SA-β-gal) staining was used to detect  cell senescence induced by Ang Ⅱ in different concentrations and at different time to determine the best inducing condition. To further explore the mechanisms, the effects of AT1 receptor blocker irbesartan and AT2 receptor blocker PD123319 on Ang Ⅱ-induced cell senescence were examined. Expressions of cell cycle-related protein P53 and P21 were detected by Western blot assay. Results   Forty-eight his incubation of Ang Ⅱ (10μmol/L)  could induce cell senescence in  primary rat hippocampal neurons. Irbesartan could  inhibit cell senescence induced by Ang Ⅱ and reduce the expression of P53 and P21, whereas PD123319 had no effect on both of them. Conclusion   Ang Ⅱ can induce cell senescence in the primary rat hippocampal neurons. The effect of Ang Ⅱ on cell senescence may be mediated by AT1 receptor and the mechanism may be related to the over-expression of protein P53 and P21.

Key words: Angiotensin Ⅱ; Hippocampus; Neuron; Cell senescence; Irbesartan; PD123319

中图分类号: 

  • R964
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