Rho kinase inhibition by fasudil exerts antioxidant effects in hypercholesterolemic rats
Rho kinase inhibition by fasudil exerts antioxidant effects in hypercholesterolemic rats
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DOI：
10.1111/j.1440-1681.2011.05561.x
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发表时间：
2011-10-01
影响因子：
2.9
通讯作者：
Chu, Li
中科院分区：
文献类型：
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作者：
Ma, Zhihong;Zhang, Jianping;Chu, Li
1. 抑制Rho激酶（ROCK）可改善多种心血管功能障碍，但ROCK在高胆固醇血症大鼠氧化应激中的作用尚未被探索。本研究的目的是探讨选择性ROCK抑制剂法舒地尔对高胆固醇饮食(HCD)诱导的高胆固醇血症大鼠的抗氧化作用及其潜在相关机制。 2．通过用 HCD 喂养 4 周，诱导大鼠出现高胆固醇血症。从第15天开始，腹腔注射生理盐水（1 mL/100 g）或ROCK抑制剂法舒地尔（10或30 mg/kg），再腹腔注射14天。 3．结果表明，法舒地尔显着抑制ROCK活性，有效升高抗氧化酶活性和内皮一氧化氮合酶表达，以及血清和心脏组织中一氧化氮浓度。此外，法舒地尔还可显着抑制高胆固醇血症大鼠的脂质过氧化程度，减轻心脏和肝脏的组织病理学变化。 4．法舒地尔的这些抗氧化作用表明 ROCK 激活与高胆固醇血症大鼠的氧化应激有关。
1. The inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions, but the role of ROCK in oxidative stress in hypercholesterolemic rats has not been explored. The aim of the current study was to investigate the antioxidant effects and the potential related mechanisms of fasudil, a selective ROCK inhibitor, in high-cholesterol diet (HCD)-induced hypercholesterolemic rats.2. Hypercholesterolemia was induced in rats by feeding with a HCD for 4 weeks. Starting from day 15, physiological saline (1 mL/100 g) or ROCK inhibitor, fasudil (10 or 30 mg/kg), was injected intraperitoneally for another 14 days.3. The results showed that fasudil significantly suppressed ROCK activity, potently elevated the activities of antioxidant enzymes and the expression of endothelial nitric oxide synthase, as well as the concentration of nitric oxide in the serum and cardiac tissue. In addition, fasudil notably suppressed the extent of lipid peroxidation and attenuated the histopathological changes in the heart and liver of hypercholesterolemic rats.4. These antioxidant effects of fasudil suggest that ROCK activation is involved in oxidative stress in hypercholesterolemic rats.