Tang Futian, Wu Xiaoqian, Wang Tieqiao, Wang Ping, Li Ruifang, Zhang Huijie, Gao Jie, Chen Shaorui, Bao Liping, Huang Heqing, Liu Peiqing
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, PR China.
Vascul Pharmacol. 2007 Jun;46(6):427-38. doi: 10.1016/j.vph.2007.01.001. Epub 2007 Jan 23.
We have previously proved that oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, plays a pivotal role in the development of atherosclerotic calcification (AC). The present study was performed to investigate whether tanshinone II A (TS II A), an anti-oxidant which has been shown to inhibit in vitro oxidation of LDL, has the effects to inhibit AC in rat model and by which, if any, mechanisms.
Rat AC model was induced by excessive vitamin D(2) (VD) and high cholesterol diet (HCD), which was proven to be successful histopathologically and biochemically.
Administration of AC rats with TS II A (35, 70 mg/kg) dose-dependently attenuated the AC pathological changes, meanwhile reduced the vessel contents of lipid and calcium. However, TS II A had no effects on serum levels of lipids, calcium and 25-OH VD. Further studies revealed that TS II A decreased serum concentration of oxLDL, reduced the superoxide anion production and malondialdehyde (MDA) in vessel. In addition, TS II A increased vessel Cu/Zn SOD activity, upregulated vessel mRNA and protein expression of Cu/Zn SOD.
The results suggested that TS II A significantly attenuated the AC in rat model, which might be attributed to its inhibition of oxLDL production independent of the serum levels of lipids, calcium and 25-OH VD, and that increasing of Cu/Zn SOD activity as well as mRNA and protein expression by TS II A might protect LDL against oxidation induced by superoxide anion in vessel.
我们之前已经证明，氧化型低密度脂蛋白（oxLDL），一种促动脉粥样硬化脂蛋白，在动脉粥样硬化钙化（AC）的发展中起关键作用。本研究旨在探讨丹参酮II A（TS II A），一种已被证明能抑制体外LDL氧化的抗氧化剂，是否具有抑制大鼠模型中AC的作用以及其作用机制（如果有的话）。
通过过量维生素D₂（VD）和高胆固醇饮食（HCD）诱导大鼠AC模型，经组织病理学和生物化学方法证实该模型构建成功。
给AC大鼠给予TS II A（35、70mg/kg）后，AC病理变化呈剂量依赖性减轻，同时降低了血管中的脂质和钙含量。然而，TS II A对血脂、血钙和25-OH VD的血清水平没有影响。进一步研究表明，TS II A降低了血清oxLDL浓度，减少了血管中超氧阴离子的产生和丙二醛（MDA）含量。此外，TS II A增加了血管Cu/Zn SOD活性，上调了血管Cu/Zn SOD的mRNA和蛋白表达。
结果表明，TS II A能显著减轻大鼠模型中的AC，这可能归因于其抑制oxLDL产生，且与血脂、血钙和25-OH VD的血清水平无关，并且TS II A增加Cu/Zn SOD活性以及mRNA和蛋白表达可能保护LDL免受血管中超氧阴离子诱导的氧化。
