Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation.
Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation.
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DOI：
10.1016/j.ijcard.2008.12.102
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发表时间：
2009-08
影响因子：
3.5
通讯作者：
Zhi-jian Guo;F. Hou;Shang-xi Liu;Jian-wei Tian;Wei Zhang;D. Xie;Zhangjin Zhou;Zhi Qiang Liu
中科院分区：
文献类型：
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作者：
Zhi-jian Guo;F. Hou;Shang-xi Liu;Jian-wei Tian;Wei Zhang;D. Xie;Zhangjin Zhou;Zhi Qiang Liu
背景晚期糖基化终末产物(AGE)或高级氧化蛋白产物(AOPP)的积累已被确定为糖尿病和慢性肾病中所见加速动脉粥样硬化的危险因素。然而，人们对与这些氧化蛋白相关的动脉粥样硬化形成的干预知之甚少。胡黄连 (Picrorhiza scrophulariiflora, PS) 的根茎长期以来作为传统药物用于治疗炎症性疾病。本研究的目的是检验乙醇提取 PS (EPS) 可能改善 AGEs 或 AOPPs 诱导的体内加速动脉粥样硬化的假设。 方法与结果 高胆固醇血症或正常兔子被随机分为 8 组，分别在存在或不存在 EPS 的情况下静脉注射 AGEs 或 AOPPs 修饰的兔血清白蛋白（AGEs-RSA 或 AOPPs-RSA）、未修饰的 RSA 或载体。 （10 mg/kg/2 天）灌胃 10 周。与未进行 EPS 治疗的高胆固醇血症兔相比，EPS 给药显着减少了高胆固醇血症动物的主动脉斑块体积和氧化低密度脂蛋白 (Ox-LDL) 沉积。伴随着显着的组织学改善，包括受影响区域内膜和平滑肌细胞增殖以及巨噬细胞流入的减少。在高胆固醇血症和正常兔子中，EPS给药几乎完全消除了由AGEs-或AOPPs-RSA长期治疗引起的加速动脉粥样硬化。 EPS 给药显着恢复了 AGEs 或 AOPPs 诱导的氧化还原失衡和炎症，表现为血浆 Ox-LDL、硫代巴比妥酸反应物质和 TNF-α 的减少以及谷胱甘肽过氧化物酶活性的增加。结论这些数据表明 EPS 可以通过抑制氧化还原敏感的炎症来改善动脉粥样硬化，特别是由 AGEs 或 AOPPs 诱导的动脉粥样硬化。
BACKGROUNDAccumulation of advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs) has been identified as a risk factor for accelerated atherosclerosis seen in diabetes and chronic kidney disease. However, little is known about the intervention for atherogenesis associated with these oxidized proteins. The rhizome of Picrorhiza scrophulariiflora (PS) has long been used to treat inflammatory diseases as a traditional medication. The study was performed to test the hypothesis that ethanol extraction of PS (EPS) may improve AGEs- or AOPPs-induced accelerated atherosclerosis in vivo.METHODS AND RESULTSHypercholesterolemic or normal rabbits were randomly assigned to 8 groups treated with intravenous injection of AGEs- or AOPPs-modified rabbit serum albumin (AGEs-RSA or AOPPs-RSA), unmodified RSA or vehicle in the presence or absence of EPS (10 mg/kg/2 days) gavage for 10 weeks. Compared with hypercholesterolemic rabbits without EPS treatment, EPS administration significantly decreased the aortic plaque volume and oxidized low density lipoprotein (Ox-LDL) deposition in hypercholesterolemic animals. This was accompanied by significant histological improvement including decrease of intimal and smooth muscle cell proliferation and macrophage influx in affected areas. EPS administration almost completely abolished the accelerated atherosclerosis induced by chronic treatment of AGEs- or AOPPs-RSA in both hypercholesterolemic and normal rabbits. EPS administration significantly restored the AGEs- or AOPPs-induced redox imbalance and inflammation, evidenced by decrease of plasma Ox-LDL, thiobarbituric acid reactive substances and TNF-α, and increase of glutathione peroxidase activity.CONCLUSIONThese data suggested that EPS may improve atherosclerosis, particularly that induced by AGEs or AOPPs, through inhibition of redox-sensitive inflammation.