CD36调控多囊卵巢综合征女性脂代谢异常的分子机制研究

It is known that the prevalence of polycystic ovarian syndrome (PCOS) has reached to 5.6 percent in Chinese community women at reproductive ages. Moreover abnormal lipid metabolism has been observed in large part of women with PCOS, which resulted in the increased incident of complications including hypertension, diabetes and cardiovascular diseases. CD36 is an upstream molecular in the signal pathway of regulating lipid metabolism, and the aberrated expression profiling of CD36 has been proved the positive role in the PCOS women with impaired lipid metabolism, however it is still unclear for its molecular mechanism in the process. In the present study, genomic transcription is studied by gene chips using muscle cells from PCOS women, and the genes related to lipid metabolism is screened and the signal pathway that regulated CD36 activity is identified. Differentiated metabolism products will be predicted by metabonomics and gene expression, and their function will be tested by cellular and animal model study to improve the phenotype of PCOS. Our project will provide the theoretical direction of PCOS etiology, and facilitate to further study of drug discovery for prevention and treatment of abnormal lipid metabolism in PCOS women.

多囊卵巢综合征（PCOS）患者在我国育龄女性人群中发病率达到5.6%，同时此类患者脂代谢异常发生率高，使其远期并发症高血压、糖尿病、心血管疾病发病率明显高于非PCOS育龄女性人群。CD36在脂类物质代谢中处于信号通路的上游，其表达异常与PCOS患者脂代谢异常密切相关，但是其作用的分子机制还不清楚。本研究拟通过高通量组学技术，研究PCOS患者肌肉细胞的转录情况，明确与脂代谢相关的差异表达基因，分析与CD36表达有相关性的调控通路，并通过动物研究，明确调控CD36表达的新转录因子的功能，并预测可能与其相关的细胞因子，进而利用细胞学与动物学实验，验证预测准确性的同时，探索是否可以通过细胞因子，达到治疗PCOS异常脂代谢病理现象的目的。我们的研究为明确PCOS病理提供了理论借鉴，同时对于寻找预防和治疗PCOS脂代谢异常的药物提供了理论指导。

多囊卵巢综合征(PCOS)患者在我国育龄女性人群中发病率达到5.6%，同时此类患者脂代谢异常发生率高，使其远期并发症高血压、糖尿病、心血管疾病发病率明显高于非PCOS育龄女性人群。PCOS是一类病因复杂的代谢类疾病，与其他类型的代谢综合征不同，PCOS代谢异常会诱发一部分女性排卵障碍，进而导致不孕症。因PCOS的诱因复杂，目前还缺乏深入的病理机制的探索，同时诊疗策略缺乏创新。本课题主要关注PCOS女性代谢异常的特征，以无排卵性不孕症女性作为研究重点，利用大规模流行病学调查数据，论证PCOS女性的代谢风险因素，并建立PPARGC1A预测PCOS女性代谢异常水平的分子标志物。同时，对PCOS女性卵巢局部开展靶向代谢组学检测，明确代谢特征的同时，对CD36，CD14，CD16等分子开展研究，阐述CD36影响PCOS女性排卵的分子途径。最终建立以PDGFRA，HSD17B4和HMGB2为潜在治疗靶点的PCOS诊疗策略。课题从整体到局部对PCOS的代谢异常的分子机制进行了详尽探讨，为继续探索PCOS代谢异常影响生育结局的分子机制奠定基础，同时为PCOS临床诊疗新策略的建立提供理论支持。