越来越多的证据表明,多囊卵巢综合征(PCOS)常伴有炎症反应,因此,适当控制颗粒细胞炎症对PCOS患者卵巢功能恢复至关重要.在这项研究中,评估了GSE34526数据集中对照和PCOS样本之间嘌呤能受体P2×7的差异水平,建立PCOS小鼠模型。在评估激素水平的波动之后,炎性细胞因子,和P2×7,小鼠接受P2×7拮抗剂A740003的治疗。它对荷尔蒙的影响,炎症,凋亡,和NOX2信号在小鼠中被检查。之后,分离原代小鼠颗粒细胞,通过转染NOX2过表达质粒证实了NOX2信号在P2×7调控途径中的介导作用。结果表明,在数据集中的PCOS样品中,P2×7显著升高。与对照组相比,PCOS小鼠卵泡刺激素有显著差异,黄体生成素,睾丸激素,抗苗勒管激素,炎症因子,和P2×7。A740003治疗部分恢复了这些参数水平,包括NOX2信令。基于原代小鼠颗粒细胞的体外实验,上述发现得到了重新验证,NOX2的过表达可以逆转P2×7的调节功能。本研究强调PCOS中P2×7水平升高,抑制P2×7可以减轻疾病症状。它通过NOX2/JNK信号传导参与颗粒细胞的炎症和凋亡。
Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor
P2X7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and
P2X7, mice received treatment with the
P2X7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2X7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that
P2X7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2X7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2X7. The present study highlights that
P2X7 level increases in PCOS, and inhibition of
P2X7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.