Ginsenoside Rb1 attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways
Ginsenoside Rb1 attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways
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DOI：
10.1016/j.vph.2015.04.003
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发表时间：
2015-10-01
影响因子：
4
通讯作者：
Wan, Jian-Bo
中科院分区：
文献类型：
--
作者：
Zhang, Xiao-Jing;He, Chengwei;Wan, Jian-Bo
背景资料：腹主动脉瘤（AAA）是一种危及生命的血管疾病，约占65岁以上人群发病率的10%。没有令人满意的方法可用于治疗AAA。人参皂苷Rb 1和Rg 1是三七的主要成分，用于治疗心血管疾病，但其对AAA的影响是unknowed.Methods和结果：AAA模型建立使用血管紧张素II输注ApoE（-/-）小鼠。连续刺激28天后，77%的小鼠发生了肾上主动脉瘤，12%的小鼠因AAA破裂而突然死亡。给予抗心律失常Rb 1（20 mg/kg/天），而不是抗心律失常Rg 1，显著降低AAA的发病率和死亡率。人参皂苷Rb 1治疗显着抑制血管紧张素II诱导的直径扩大，细胞外基质降解，基质金属蛋白酶（MMP）的生产，炎症细胞浸润，血管平滑肌细胞（VSMC）功能障碍。机制研究表明，JNK和p38 MAPK信号通路的失活与JNK和p38 MAPK的保护作用有关。结论：人参皂苷Rb 1可能通过抑制JNK和p38信号通路抑制AAA的发生。(C)2015 Elsevier Inc. All rights reserved.
Background: Abdominal aortic aneurysm (AAA), a life-threatening vascular disease, accounts for approximately 10% of the morbidity in people over 65 years old. No satisfactory approach is available to treat AAA. Ginsenosides Rb1 and Rg1 are primary ingredients of Panax notoginseng for the treatment of cardiovascular diseases, but their impact on AAA is unknown.Methods and results: An AAA model was established using an Ang II infusion in ApoE(-/-) mice. After continuous stimulation of Ang II for 28 days, suprarenal aortic aneurysms developed in 77% mice and 12% mice died suddenly due to AAA rupture. Administration of ginsenoside Rb1 (20 mg/kg/day), but not ginsenoside Rg1, significantly reduced the incidence and mortality of AAA. Ginsenoside Rb1 treatment dramatically suppressed Ang II-induced diameter enlargement, extracellular matrix degradation, matrix metalloproteinase (MMP) production, inflammatory cell infiltration, and vascular smooth muscle cell (VSMC) dysfunction. Mechanistic studies indicated that the protective effects of ginsenoside Rb1 were associated with the inactivation of JNK and p38 MAPK signaling pathways. A specific activator of JNK and p38, anisomycin, nearly abolished ginsenoside Rb1-driven suppression of MMP secretion by VSMCs.Conclusions: Ginsenoside Rb1, as a potential anti-AAA agent, suppressed AAA through inhibiting the JNK and p38 signaling pathways. (C) 2015 Elsevier Inc. All rights reserved.