lncRNA SRA通过MEK-ERK/GATA4/miR-29a-3p轴调控SGMS2在多囊卵巢综合征慢性炎症中的机制研究

多囊卵巢综合征（PCOS）是妇女常见的内分泌异常疾病，低度慢性炎症与胰岛素抵抗为其普遍特征。lncRNA SRA在PCOS患者中表达上调，可激活MEK-ERK，MEK-ERK通路可活化转录因子GATA4调控基因表达。miR-29a-3p启动子区存在GATA4结合位点，GATA4可抑制miR-29a-3p表达。生信预测显示鞘磷脂合成酶SGMS2是miR-29a-3p的靶基因，可活化NF-κB导致炎症。前期研究发现，鞘磷脂在PCOS患者中表达上调，补肾化痰复方增加PCOS胰岛素敏感性，且高胰岛素抵抗患者体内鞘磷脂减少。综上，我们提出科学假说：lncRNA SRA通过MEK-ERK通路激活GATA4，抑制miR-29a-3p表达，SGMS2表达上调，催化合成鞘磷脂，NF-κB活化，促进PCOS低度慢性炎症。探讨补肾化痰方治疗PCOS分子机制，为临床诊断PCOS和研发治疗药物提供理论基础。

Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disorder in women. Low-grade chronic inflammation and insulin resistance are common characteristics of PCOS. lncRNA SRA is up-regulated in PCOS patients. lncRNA SRA can activate the MEK-ERK signaling pathway, which can activate the transcription factor of GATA4 to regulate the transcriptional expression of genes. There are bingding sites of GATA4 in the promoter region of miR-29a-3p, which can inhibit the expression of miR-29a-3p. The Bioinformatics website predicted that SGMS2 is a target gene of miR-29a-3p, and SGMS2 is a key enzyme for sphingomyelin synthesis, that can activate NF-κB and lead to inflammatory response. Previous studies have found that sphingomyelin is up-regulated in PCOS patients, The Bushen Huatan Formula could increase insulin sensitivity in patients with PCOS, and the content of sphingomyelin in patients with high insulin resistance was significantly reduced.In conclusion, we propose a scientific hypothesis that lncRNA SRA activates the transcription factor of GATA4 through the MEK-ERK pathway, thereby inhibiting the expression of miR-29a-3p, leading to the up-regulation of SGMS2, catalyzing the synthesis of sphingomyelin, activation of NF-κB, and promoting the inflammation of PCOS. In addition, to explore molecular mechanism of Bushen Huatan Formula for treating PCOS. It provides theoretical basis and therapeutic targets for clinical diagnosis of PCOS and development of therapeutic drugs.