Department of Anesthesiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Phytother Res. 2011 May;25(5):732-9. doi: 10.1002/ptr.3331. Epub 2010 Nov 12.
The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics, cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1 (ASK1) and nuclear factor-κB (NF-κB) cascades in isoproterenol (Iso)-induced cardiac remodelling (CR) rat model were investigated, in addition, the serum SOD activities and MDA content were assayed. Rats were treated with Iso to induce CR and were given distilled water or GSP for 1 week. Control rats received vehicle instead of Iso. Administration of GSP markedly alleviated the elevation of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in the heart, and improved the haemodynamic index. Meanwhile, treatment with GSP significantly ameliorated oxidative stress by improving SOD activities and decreasing MDA formation. Moreover, GSP apparently inhibited the expression ASK1, NF-κB and its targeted gene - COX-2. These findings suggest that administration of GSP has the potential to attenuate Iso-induced CR by repressing oxidative stress and inhibiting the activation of the cellular signaling cascades involving the ASK1 and NF-κB pathways, at least in part, providing a molecular mechanism for the cardioprotective effect of GSP.
研究了低聚原花青素（GSP）对异丙肾上腺素（Iso）诱导的心脏重构（CR）大鼠模型血流动力学、心肌肥厚和纤维化以及凋亡信号调节激酶 1（ASK1）和核因子-κB（NF-κB）级联的影响，此外，还测定了血清 SOD 活性和 MDA 含量。大鼠用 Iso 诱导 CR，并给予蒸馏水或 GSP 治疗 1 周。对照组大鼠给予载体而不是 Iso。GSP 的给药显著减轻了左心室重量（LVW）/体重（BW）、心脏重量（HW）/体重（BW）比值和心肌细胞横截面积的升高，减少了心脏中的胶原沉积，并改善了血流动力学指数。同时，GSP 通过提高 SOD 活性和减少 MDA 形成明显改善了氧化应激。此外，GSP 明显抑制了 ASK1、NF-κB 及其靶向基因 - COX-2 的表达。这些发现表明，GSP 的给药具有通过抑制涉及 ASK1 和 NF-κB 途径的细胞信号级联的氧化应激和激活来减轻 Iso 诱导的 CR 的潜力，至少部分提供了 GSP 的心脏保护作用的分子机制。
