Abstract：
Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE-/- mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE-/- mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67-7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.
摘要：
巨噬细胞脂质积累表明动脉粥样硬化的病理变化。IlexgeninA(IA),五环三萜类化合物，在预防炎症中起作用，细菌感染,和脂肪肝，并诱导潜在的抗动脉粥样硬化作用。然而,抗动脉粥样硬化机制尚不清楚.本研究调查了IA对apoE-/-小鼠巨噬细胞源性泡沫细胞中脂质积累和动脉粥样硬化的影响。我们的结果表明，三磷酸腺苷结合盒转运蛋白A1（ABCA1）的表达被IA上调，促进胆固醇流出和减少巨噬细胞中的脂质积累，可能受蛋白酪氨酸磷酸酶非受体2型（PTPN2）/ERK1/2信号通路的调节。IA在高脂饮食喂养的apoE-/-小鼠中减弱了动脉粥样硬化的进展。用siRNA敲低PTPN2或用ERK1/2激动剂(Ro67-7476)处理阻碍IA对巨噬细胞中ABCA1上调和胆固醇流出的影响。这些结果表明IA通过PTPN2/ERK1/2信号通路抑制巨噬细胞脂质积累并减轻动脉粥样硬化进展。
