PDF(Pubmed)
Abstract：
UNASSIGNED: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.
摘要：
动脉粥样硬化（AS）是由多种因素引起的慢性进行性疾病，可引起各种脑血管和心血管疾病（CVD）。降低血浆低密度脂蛋白胆固醇（LDL-C）水平是预防和治疗AS的主要目标。前蛋白转化酶枯草杆菌蛋白酶/Kexin9型（PCSK9）在调节LDL-C代谢中起着至关重要的作用。三七具有有效的降脂作用，可以预防心血管疾病，其皂苷诱导血管扩张，抑制血栓形成，用于治疗心血管疾病。然而,次级代谢产物的抗AS作用，20（S）原人参三醇（20（S）-PPT），尚不清楚。在这项研究中,采用免疫印迹法研究了20(S)-PPT的体内、体外抗AS作用及分子机制,实时聚合酶链反应（RT-PCR），酶联免疫吸附测定(ELISA),免疫荧光染色，和其他化验。体外实验表明,20(S)-PPT降低了HepG2细胞上清液中PCSK9的水平,低密度脂蛋白受体（LDLR）蛋白水平上调，通过HepG2细胞促进LDL摄取，并通过上调FoxO3蛋白和mRNA的水平以及降低HNF1α和SREBP2蛋白和mRNA的水平来降低PCSK9mRNA的转录。体内实验显示20(S)-PPT上调主动脉αSMA表达,增加了动脉粥样硬化斑块的稳定性，在ApoE-/-小鼠（HCF组）中，高胆固醇喂养引起的主动脉斑块形成减少。此外,20（S）PPT降低CD68的主动脉表达，减轻主动脉根部的炎症，减轻HCF组的肝脏病变。研究表明，20（S）-PPT通过PCSK9抑制LDLR降解以减轻AS。
