Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.
Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.
Inflammation. 2017 Oct;40(5):1631-1642. doi: 10.1007/s10753-017-0603-8.
Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE mice with P. gingivalis infection. Eight-week-old ApoE mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg day). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects.
丹参酮 IIA（TSA）是从丹参中分离得到的一种具有药理活性的成分，由于其具有抗炎、抗氧化和抗脂肪生成作用，可能预防心血管疾病。牙龈卟啉单胞菌是一种主要的牙周病原体，可能导致动脉粥样硬化的进展。在这里，我们研究了 TSA 对感染牙龈卟啉单胞菌的 ApoE 小鼠动脉粥样硬化的影响。将 8 周龄的 ApoE 小鼠随机分为（a）磷酸盐缓冲液（PBS），（b）牙龈卟啉单胞菌和（c）牙龈卟啉单胞菌+ TSA（60mgkg 天）。每周向小鼠注射（a）PBS，或（b）和（c）牙龈卟啉单胞菌 3 次，共 10 次。8 周后，用油红 O、动脉粥样硬化细胞因子抗体阵列、酶联免疫吸附试验（ELISA）、实时 PCR 和 microRNA 阵列分析所有小鼠血清和心脏、主动脉和肝脏组织中的动脉粥样硬化危险因素。在动脉粥样硬化细胞因子抗体阵列中，TSA 减弱了 CD40、G-CSF、IFN-γ、白细胞介素（IL）-1β、IL-6、MCP-1、MIP-3α、肿瘤坏死因子-α（TNF-α）和 VEGF。TSA 处理的小鼠在 ELISA 数据中显示 C 反应蛋白（CRP）、氧化低密度脂蛋白（ox-LDL）、IL-1β、IL-6、IL-12 和 TNF-α显著减少。实时 PCR 分析表明，TSA 降低了心脏和主动脉组织中 CCL-2、CD40、IL-1β、IL-6、TNF-α和 MMP-2 的表达。此外，尽管 FASN 和 HMG-CoA 没有，TSA 也下调了肝 CRP。牙龈卟啉单胞菌感染上调了 miR-146b 和 miR-155 的相对表达，而 TSA 处理则下调了其表达。这些结果表明，TSA 可能是一种潜在的治疗药物，具有通过抗炎和抗氧化作用预防牙龈卟啉单胞菌诱导的动脉粥样硬化的能力。
