Mao Qing-Qiu, Ip Siu-Po, Ko Kam-Ming, Tsai Sam-Hip, Zhao Ming, Che Chun-Tao
School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Cell Mol Neurobiol. 2009 Jul;29(5):643-7. doi: 10.1007/s10571-009-9357-7. Epub 2009 Feb 12.
Preclinical and clinical investigations have shown the involvement of dysregulation of hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of depression. Hypercortisolemia and the associated hippocampal atrophy were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Previous studies in our laboratory have demonstrated the antidepressant-like activity of total glycosides of peony (TGP) in mice. This study aimed to examine the effect of TGP treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Treating the cells with corticosterone at 200 muM for 48 h caused apoptotic cell death. The cytotoxicity was associated with the activation of caspase-3 activity and the decrease in the mRNA ratio of bcl-2 to bax. TPG treatment at increasing doses (1-10 mg/l) protected against the corticosterone-induced toxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with the inhibition of caspase-3 activity and the up-regulation of bcl-2/bax mRNA ratio. The anti-apoptotic effect of TGP is therefore likely mediated by the suppression of the mitochondrial pathway leading to apoptosis.
临床前和临床研究表明，下丘脑-垂体-肾上腺（HPA）轴调节异常参与了抑郁症的发病机制。在抑郁症患者中观察到高皮质醇血症及相关的海马萎缩，而抗抑郁药治疗可使其改善。因此，神经保护作用被认为是抗抑郁药的作用机制之一。我们实验室之前的研究已证明芍药总苷（TGP）在小鼠中有类抗抑郁活性。本研究旨在检测TGP处理对培养的大鼠嗜铬细胞瘤（PC12）细胞中皮质酮诱导的神经毒性的影响。用200μM皮质酮处理细胞48小时会导致凋亡性细胞死亡。细胞毒性与半胱天冬酶-3活性的激活及bcl-2与bax mRNA比例的降低有关。递增剂量（1-10mg/l）的TPG处理以剂量依赖性方式保护PC12细胞免受皮质酮诱导的毒性。TGP处理提供的细胞保护作用与半胱天冬酶-3活性的抑制及bcl-2/bax mRNA比例的上调有关。因此，TGP的抗凋亡作用可能是通过抑制导致凋亡的线粒体途径介导的。
