Rutaecarpine prevents Ang II -induced vascular smooth muscle cell senescence through TRPV1/ SIRT1 pathway / 中国药理学通报

ABSTRACT

Aim To evaluate the effects of Rutaecarpine(Rut)on the expression of SIRT1 and the senescence of vascular smooth muscle cells(VSMCs)induced by angiotensin Ⅱ.Methods VSMC senescencewas induced by exposure to AngⅡ(1 μmol·L-1)for 72 h.VSMCs were treated with different concentrations of Rut(0.3, 1, 3 μmol·L-1).TRPV1 competitive antagonist CAPZ(10 μmol·L-1)and AMPK inhibitor Compound C(1 μmol·L-1)were used to explore whether TRPV1/AMPK mediated the protective effect of Rut.The quantity of senescent cells were determined by senescence-associated SA-β-Gal staining, and the intracellular ROS level was measured by(DCFH-DA)fluorescent probe.The migration ability of VSMCs was evaluated by Wound-healing assay combined with Transwell assay.The protein level of longevity protein SIRT1 and senescence-related proteins p53, p21 and AMPK phosphorylation level were detected by Western blot.Results Rut significantly inhibited Ang Ⅱ-induced VSMC senescence and ROS production and prevented VSMCs migration.Preprocessing of TRPV1 antagonist CAPZ could abolish the protective effect of Rut.Ang Ⅱ inhibited the expression of longevity protein SIRT1.Rut recovered SIRT1 expression in a dose-dependent manner, while prevented the up-regulation of senescence-related proteins p53 and p21.Ang Ⅱ inhibited AMPK phosphorylation, pre-treatment with Rut restored AMPK phosphorylation level.CAPZ and Compound C eliminated the up-regulating function of Rut on SIRT1 expression.Conclusions Rut up-regulates the expression of SIRT1 and prevents the senescence and migration of VSMCs induced by Angiotensin Ⅱ, which is related to activation of the TRPV1/AMPK signaling pathway.