Xuan Yan, Yu Cai, Ni Kang, Congcong Lou, Lixin Qiu, Qingxian Luan
Department of the Fourth Division, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
Department of Periodontology, Peking University, School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
Microbes Infect. 2023 Nov-Dec;25(8):105177. doi: 10.1016/j.micinf.2023.105177. Epub 2023 Jun 29.
Tanshinone IIA (TSA), an active component isolated from Danshen, possess high medicinal values against atherosclerosis by reducing vascular oxidative stress, inhibiting platelet aggregation, and protecting the endothelium from damage. The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has been proven to accelerate the development of atherosclerosis. We aim to determine the effects of TSA on P. gingivalis-induced atherosclerosis in ApoE-knockout (ApoE-/-) mice. After feeding with a high-lipid diet and infected with P. gingivalis three times per week for four weeks, TSA-treated (60 mg/kg/d) mice greatly inhibited atherosclerotic lesions both morphologically and biochemically and exhibited significantly reduction ROS, 8-OHdG, and ox-LDL levels in serum compared with P. gingivalis-infected mice. Additionally, TSA-treated mice were observed a marked reduction of ROS, 8-OHdG and ox-LDL in the serum, mRNA levels of COX-2, LOX-1, NOX2 and NOX4 in the aorta, as well as the levels of NOX2, NOX4, and NF-κB. These results suggest that TSA attenuates oxidative stress by decreasing NOX2 and NOX4 and downregulating NF-κB signaling pathway, which might be contributed to the amelioration of atherosclerosis.
丹参酮IIA（TSA）是从丹参中分离出的一种活性成分，通过降低血管氧化应激、抑制血小板聚集以及保护内皮免受损伤，对动脉粥样硬化具有很高的药用价值。牙周病原体牙龈卟啉单胞菌（P. gingivalis）已被证明会加速动脉粥样硬化的发展。我们旨在确定TSA对载脂蛋白E基因敲除（ApoE-/-）小鼠中牙龈卟啉单胞菌诱导的动脉粥样硬化的影响。在给予高脂饮食并每周感染三次牙龈卟啉单胞菌，持续四周后，与感染牙龈卟啉单胞菌的小鼠相比，TSA处理组（60 mg/kg/d）小鼠在形态学和生物化学方面均极大地抑制了动脉粥样硬化病变，并且血清中的活性氧（ROS）、8-羟基脱氧鸟苷（8-OHdG）和氧化型低密度脂蛋白（ox-LDL）水平显著降低。此外，在TSA处理的小鼠中观察到血清中的ROS、8-OHdG和ox-LDL显著减少，主动脉中环氧合酶-2（COX-2）、凝集素样氧化低密度脂蛋白受体-1（LOX-1）、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（NOX2）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（NOX4）的mRNA水平，以及NOX2、NOX4和核因子κB（NF-κB）的水平均降低。这些结果表明，TSA通过降低NOX2和NOX4并下调NF-κB信号通路来减轻氧化应激，这可能有助于改善动脉粥样硬化。
