Y染色体上LncRNA TXLNGY吸附miR-17上调ACSL4促进TAO内皮细胞铁死亡的机制研究

血栓闭塞性脉管炎（Thromboangiitis obliterans，TAO）是一种致残率极高的难治性血管闭塞性疾病，至今发病机制不清，LncRNA是否起作用未见报道。该病明显好发于男性，病因不清。我们预实验通过对TAO临床样本的高通量RNA测序及相关指标的检测，提示铁死亡可能参与TAO的发病过程。 进一步筛选到位于Y染色体上的LncRNA TXLNGY可能是影响内皮细胞铁死亡的关键因子，提出假说：在TAO发病过程中，TXLNGY通过miRNA sponge机制吸附miR-17，促进铁死亡关键蛋白ACSL4表达，从而促进内皮细胞发生铁死亡。本项目拟通过RIP，电子显微镜、CRISPR基因编辑等技术，进一步明确铁死亡是否参与TAO，并验证上述假说是否成立，初步探索铁死亡抑制剂对TAO治疗效应。本项目可以纵向深入研究TAO的发病机制与男性偏好性的关联及认识，为促进TAO诊断与治疗提供参考

It is know that Thromboangiitis obliterans (TAO) is a refractory vascular occlusive disease with a very high disability rate. Up to now, The disease is significantly more common in men with it cause is unclear, and the disease pathogenesis is unclear, whether lncRNA plays a role has not been reported. It is showed that ferroptosis might be involved in the pathogenesis of TAO in our pre-experiment through high-throughput RNA sequencing of TAO clinical samples and detection of related indicators. It was further screened that lncRNA TXLNGY on Y chromosome might be the key factor affecting ferroptosis of endothelial cells. Based on the results of pre experiment, the hypothesis was put forward that TXLNGY adsorbed miR-17 through miRNA sponge mechanism during the pathogenesis of TAO, and promoted the expression of ACSl4, the key protein of ferroptosis, so as to promote ferroptosis of endothelial cells. This project intends to rip, electron microscopy and CRISPR gene editing techniques for verifing whether the above hypothesis holds.It used to further clarify whether ferroptosis is involved in TAO, and to verify whether the above hypothesis is true, so as to preliminarily explore the therapeutic effect with ferroptosis inhibitors on TAO. This project can study the relationship between the pathogenesis of TAO and gender preference, and provide basic scientific research and reference for the development of TAO diagnosis and treatment.