Abstract：
We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.
摘要：
我们探讨了雌激素和PCSK9之间的相互作用及其对脂质代谢的集体影响，尤其是低密度脂蛋白受体水平的调节。利用动物和细胞模型，包括卵巢切除小鼠和HepG2细胞系，我们证明雌激素缺乏导致脂质代谢中断，以总胆固醇和LDL-C水平升高为特征这项研究从接受卵巢切除术的小鼠开始，然后是包括高脂肪饮食或正常饲料的饮食方案，持续四周。关键评估包括分析脂质代谢，测量血液中的PCSK9水平，并评估肝脏低密度脂蛋白受体的表达。我们还将进行相关性分析，以了解PCSK9和各种血脂谱之间的关系。Further,一部分接受高脂饮食的卵巢切除小鼠将接受雌激素或PCSK9抑制剂治疗两周，随后对前面提到的参数进行重新评估。我们的研究结果表明，雌激素抑制PCSK9介导的低密度脂蛋白受体的降解，对维持脂质稳态至关重要的过程。通过一系列的实验,包括免疫组织化学和蛋白质印迹分析，我们确定PCSK9参与雌激素缺乏引起的脂质代谢紊乱,雌激素在转录后水平调节PCSK9和低密度脂蛋白受体.该研究为PCSK9参与阐明由围绝经期和卵巢衰退引起的雌激素缺乏引起的脂质代谢紊乱提供了机制。
