多囊卵巢综合征中leptin抵抗与CRP之间的关系

Insulin resistance has been proposed to play an important role in the pathogenesis of the polycystic ovary syndrome (PCOS). C-reactive protein (CRP), as the prototypic acute phase reactant after an inflammation evoking injury, has been correlated with insulin resistance. Our latest studies have shown that some adipokine were associated with insulin resistance in women with PCOS. However, the causal link between CRP and PCOS and the precise mechanism involved are remain to be elucidated. Furthermore, circulating CRP binds to leptin and may attenuates its physiological functions of hepatic glucose metabolism in PCOS are also unknown. Thus, the fully roles of CRP in the hepatic glucose metabolism in PCOS were demonstrated by using the CRP gene knockout rat. Moreover, the peripheral and central administration of leptin in hepatic glucose production were investigated by using isotope tracer, we sought to confirm that the relationship between the leptin resistance and CRP in PCOS. Then, we measured the activity of insulin signaling molecule by western blot to clarify the signaling pathways involved in the effects of leptin on the hepatic glucose metabolism in PCOS. This project is of potential importance in preventment and therapy with PCOS and its related metabolic diseases.

胰岛素抵抗是多囊卵巢综合征(PCOS)的重要特点之一。C反应蛋白(CRP)作为机体炎症损伤的急性时相反应蛋白，在胰岛素抵抗的发生发展中发挥着重要的作用。我们前期主要研究了一些脂肪因子与PCOS患者胰岛素抵抗的关系。但目前国内外研究对炎症因子CRP在PCOS中的发生发展中的作用机理并不清楚，且CRP与脂肪因子-leptin相互作用对PCOS机体糖代谢的影响亦不明确。因此，本项目通过利用CRP基因敲除大鼠构建PCOS模型，证实CRP在PCOS发生发展中的作用；结合同位素示踪技术，分析外周及中枢leptin输注对PCOS模型之CRP基因敲除大鼠肝脏葡萄糖代谢的影响；证实PCOS中leptin抵抗与CRP之间的关系；最后通过检测胰岛素信号通路关键分子的活性，解析leptin调节PCOS大鼠肝脏糖代谢的信号转导机制。研究结果将为PCOS相关代谢性疾病的预防或治疗提供一定的实验基础及理论支持。

胰岛素抵抗是多囊卵巢综合征(PCOS)的重要特点之一。C反应蛋白(CRP)作为机体炎症损伤的急性时相反应蛋白，在PCOS胰岛素抵抗的发生发展中发挥着重要的作用。本项目通过构建CRP基因敲除大鼠PCOS模型，将中枢第三脑室微量给药系统和扩展胰岛素钳夹技术相结合,并利用3-[3H]葡萄糖示踪技术及分子生物学方法，分别探讨了外周及中枢leptin输注对PCOS模型之CRP基因敲除大鼠肝脏葡萄糖代谢的影响；该研究基本按计划完成了leptin信号对CRP基因缺失之PCOS大鼠糖代谢影响；在此基础上，进一步分析leptin抵抗与CRP之间的关系。