LncRNA H19/HDAC/PUMA信号轴介导脊髓神经元细胞焦亡参与神经源性间歇性跛行发生的作用机制研究

神经源性间歇性跛行（NIC）是困扰腰椎管狭窄症患者的主要症状，由于其病理机制不清，尚缺乏确切有效的保守治疗方法，后期往往需要手术治疗，深入研究NIC发生发展分子机制具有重要意义。课题组前期工作表明，腰椎管狭窄致NIC大鼠模型中PUMA表达上调能够促进脊髓细胞凋亡，与NIC的发生发展密切相关，而其中具体的分子机制尚待我们进一步研究。根据我们前期研究基础和文献调研提出假说：LncRNA H19/HDAC/PUMA信号轴通过介导NLRP3炎症小体通路调控脊髓神经元细胞焦亡，参与NIC的发生发展。本研究拟通过课题组成熟的新型NIC大鼠模型，验证LncRNA H19/HDAC/PUMA信号轴在调控脊髓神经元细胞焦亡中的作用及其分子机理，将进一步明确对NIC病理机制的认知，为临床应用生物标志物治疗腰椎管狭窄症提供理论和实践依据。

Neurogenic intermittent claudication (NIC) caused by lumbar spinal stenosis is a common symptom in middle-aged as well as elderly patients. Due to its indistinct pathological mechanism, there is still a lack of effective treatment methods rather than conservative treatment, and surgical treatment is frequently required in the later stage. A comprehensive study on the molecular mechanism of the occurrence and development of NIC will have a great significance. The preliminary work of the research group has shown that the up-regulation of PUMA expression in the NIC rat model can promote the apoptosis of spinal cord cells, which is closely related to the occurrence and development of NIC, and the specific molecular mechanism remains to be further studied. According to our previous research and literature study, we proposed a hypothesis: LncRNA H19/HDAC/PUMA signaling pathway regulates the pyroptosis of spinal cord neurons by mediating the NLRP3 inflammation pathway, which leads to the occurrence and development of NIC. Our study intends to verify the role of LncRNA H19/HDAC/PUMA signaling pathway in the regulation of spinal cord neuronal pyroptosis and its molecular mechanism through the mature new NIC rat model of the research group, which will further clarify the understanding of the pathological mechanism of NIC and provide a theoretical and practical basis for the clinical application of biomarkers in the treatment of NIC.