Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University (HEMC), 132 East Wai-huan Road, Guangzhou, Guangdong, China.
Arch Biochem Biophys. 2011 Nov;515(1-2):72-9. doi: 10.1016/j.abb.2011.08.006. Epub 2011 Aug 26.
Tanshinone II-A (Tan), a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen), possesses anti-oxidant and anti-inflammatory activities. The present study investigated whether Tan can decrease and stabilize atherosclerotic plaques in Apolipoprotein-E knockout (ApoE(-/-)) mice maintained on a high cholesterol diet (HCD). Six week-old mice challenged with a HCD were randomly assigned to 4 groups: (a) C57BL/6J; (b) ApoE(-/-); (c) ApoE(-/-)+Tan-30 (30 mg/kg/d); (d) ApoE(-/-)+Tan-10 (10mg/kg/d). After 16 weeks of intervention, Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and en face aorta. Furthermore, immunohistochemical analysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by reduced necrotic cores, decreased macrophage infiltration, and increased smooth muscle cell and collagen contents. Tan also significantly reduced in situ superoxide anion production, aortic expression of NF-κB and matrix metalloproteinase-9 (MMP-9). In vitro treatment of RAW264.7 macrophages with Tan significantly suppressed oxidized LDL-induced reactive oxygen species production, pro-inflammatory cytokine (IL-6, TNF-α, MCP-1) expression, and MMP-9 activity. Tan attenuates the development of atherosclerotic lesions and promotes plaque stability in ApoE(-/-) mice by reducing vascular oxidative stress and inflammatory response. Our findings highlight Tan as a potential therapeutic agent to prevent atherosclerotic cardiovascular diseases.
丹参酮 II-A（Tan）是从丹参（Danshen）中分离得到的一种生物活性二萜，具有抗氧化和抗炎作用。本研究旨在探讨 Tan 是否可以减少和稳定高胆固醇饮食（HCD）维持的载脂蛋白 E 基因敲除（ApoE（-/-））小鼠的动脉粥样硬化斑块。6 周龄的 HCD 挑战小鼠被随机分为 4 组：（a）C57BL/6J；（b）ApoE（-/-）；（c）ApoE（-/-）+Tan-30（30mg/kg/d）；（d）ApoE（-/-）+Tan-10（10mg/kg/d）。干预 16 周后，Tan 治疗组小鼠主动脉窦和全主动脉粥样硬化病变面积减小。此外，免疫组织化学分析显示，Tan 使病变组成更稳定，表现为坏死核心减少、巨噬细胞浸润减少、平滑肌细胞和胶原含量增加。Tan 还显著减少主动脉原位超氧阴离子产生、NF-κB 和基质金属蛋白酶-9（MMP-9）的表达。体外用 Tan 处理 RAW264.7 巨噬细胞可显著抑制氧化型 LDL 诱导的活性氧产生、促炎细胞因子（IL-6、TNF-α、MCP-1）表达和 MMP-9 活性。Tan 通过减少血管氧化应激和炎症反应，减轻 ApoE（-/-）小鼠动脉粥样硬化病变的发展，促进斑块稳定。我们的研究结果强调了 Tan 作为预防动脉粥样硬化性心血管疾病的潜在治疗药物的作用。
