参芪胶囊通过TLR4/MyD88/NF-κB通路调控多囊卵巢综合征伴胰岛素抵抗的机制研究

We have proved that SQC can not only improve the abnormal glucose and lipid metabolism of PCOS patients, but also reduce the insulin resistance index. Further studies have shown that SQC can reduce the expression of IL-6, TNF-α protein and mRNA in PCOS rats. In addition, the binding of TLR4 with ligand can activate NF-κB inflammatory factors, resulting in chronic inflammation. Therefore, we speculated a new mechanism for SQC improving PCOS insulin resistance for the first time. SQC can improve the activity of INSR tyrosine kinase, promote the synthesis of IRS-1, activate the INS signaling pathway and inhibit the formation of PCOS insulin resistance by down-regulating the TLR4/MyD88/NF-κB signaling pathway and inhibiting the expression of inflammatory factors. Therefore, this topic proposed on the basis of previous studies to establish animal model of PCOS insulin resistance and fat cells induced insulin resistance model, application qRT-PCR, Western Blot and other molecular biology method, illustrate the SQC improve PCOS rats function and the relationship between inflammation and insulin resistance, provides new thinking for PCOS related diseases prevention and intervention measures.

前期研究证实参芪胶囊(SQC)既能改善多囊卵巢综合征(PCOS)患者的糖脂代谢异常，同时还能降低胰岛素抵抗指数，进一步研究表明SQC可降低PCOS大鼠IL-6、TNF-α蛋白和mRNA的表达。此外TLR4与配体结合后，可激活NF-κB产生炎症因子，从而导致机体处于慢性炎症状态。由此，我们推测SQC改善PCOS胰岛素抵抗的机制是通过下调TLR4/MyD88/NF-κB信号通路，抑制炎性因子的表达，改善胰岛素受体(INSR)酪氨酸激酶活性，并促进胰岛素受体底物1(IRS-1)合成，使INS信号通路激活，抑制PCOS胰岛素抵抗的形成。故本课题拟在前期研究基础上，建立PCOS胰岛素抵抗动物模型和脂肪细胞诱导胰岛素抵抗细胞模型，应用qRT-PCR、Western blot等分子生物学手段，阐明SQC改善大鼠PCOS胰岛素抵抗的作用及其与炎症之间的关系，为PCOS相关疾病的防治提供新的思路和干预措施。

多囊卵巢综合征(PCOS)是一种常见的内分泌疾病，主要影响育龄妇女。但由于多囊卵巢综合征的病因不明，其有效治疗尚不明确。参芪胶囊(SQC)由广东省中医院研制，用于治疗包括多囊卵巢综合征在内的妇科疾病已有十几年的历史。然而，SQC对PCOS的缓解作用及潜在机制仍需进一步阐明。本实验研究SQC对脱氢表雄酮(DHEA)诱导的PCOS大鼠模型的治疗作用，并进一步探讨其作用机制。结果表明，给药SQC可显著抑制PCOS大鼠体重和卵巢的增加，恢复激素水平，改善胰岛素抵抗至正常状态。组织病理学分析也证实SQC可改善DHEA诱导的卵巢损伤。此外，我们还发现SQC可显著抑制PCOS大鼠促炎细胞因子的释放，降低脂质过氧化。进一步研究证实SQC治疗PCOS大鼠可抑制卵巢组织核转录因子-κB (NF-κB)信号的激活和铁死亡。说明SQC对脱氢表雄酮诱导的PCOS大鼠有明显的治疗作用。其对PCOS的保护机制与抑制NF-κB信号和铁死亡缓解炎症和脂质过氧化密切相关。