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