Zhou Li, Zheng Yu, Li Zhuoying, Bao Lingxia, Dou Yin, Tang Yuan, Zhang Jianxiang, Zhou Jianzhi, Liu Ya, Jia Yi, Li Xiaohui
Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China.
Department of pharmacy, Xinqiao Hospital & The Second Affiliated Hospital, Third Military Medical University, Shapingba, Chongqing 400037, China.
Int J Mol Sci. 2016 Jul 8;17(7):1054. doi: 10.3390/ijms17071054.
Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti-antherosclerosis roles of compound K.
We treated the atherosclerotic model animals (apoE(-/-) mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments.
Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRα may contribute to the athero-protective effects of compound K.
These observations provide evidence for an athero-protective effect of compound K via LXRα activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis.
动脉粥样硬化是引发一些严重心血管事件的基本病理过程。尽管降胆固醇药物被广泛用于动脉粥样硬化治疗，但它仍是发达国家的主要死因。在此，我们测定了化合物K在动脉粥样硬化形成中的作用，并研究了化合物K抗动脉粥样硬化作用的可能机制。
我们用化合物K处理动脉粥样硬化模型动物（采用西式饮食的载脂蛋白E基因敲除小鼠），并测定动脉粥样硬化病变大小、炎性细胞因子水平和血脂谱。体外收集腹腔巨噬细胞用于泡沫细胞和炎性小体实验。
我们的结果表明，通过激活胆固醇逆向转运途径、降低全身炎性细胞因子水平以及抑制局部炎性小体活性，化合物K处理可使动脉粥样硬化斑块形成剂量依赖性地减少55%。化合物K增加巨噬细胞源性泡沫细胞的胆固醇流出，并降低胆固醇晶体刺激的巨噬细胞中的炎性小体活性。肝X受体α（LXRα）的激活可能有助于化合物K的抗动脉粥样硬化作用。
这些观察结果为化合物K通过激活LXRα产生抗动脉粥样硬化作用提供了证据，并支持将其作为预防和治疗动脉粥样硬化的潜在有效调节剂进行进一步评估。
