幽门螺杆菌（HP）感染与糖尿病神经病理性疼痛（PDN）密切相关，但机制不清。我们建立HP感染的PDN（HPD）大鼠模型，发现脊髓lncRNA-Noteg1表达上调，并初步鉴定其来源于HP感染胃源性外泌体。我们前期还证实mTOR表达上调是PDN发病的重要机制，而生物信息学分析并结合他人研究发现lncRNA-Noteg1存在阻遏蛋白Rbfox1负性调节mTOR pre-mRNA可变剪接的结合模体，可解除其阻遏作用。由此，我们提出HP感染胃源性外泌体lncRNA-Noteg1可通过结合Rbfox1促进mTOR pre-mRNA可变剪接，上调脊髓mTOR的表达，是导致PDN痛觉敏化的新机制。本项目应用RIP实验、RNA-pull down结合过表达/干扰慢病毒转染及电生理等技术手段验证以上科学假说，为阐明HP感染参与PDN发病的具体机制和确立lncRNA-Noteg1作为PDN新靶标提供科学依据。

Helicobacter pylori (HP) infection is closely bound up with painful diabetic neuropathy (PDN), but the specific mechanism is unclear. We established a rat model of HP infection-mediated painful diabetic neuropathy (HPD), and uncovered that novel lncRNA-Noteg1 was up-regulated in the spinal cord of HPD rats, which has been preliminarily identified that it originated from HP-infected gastrogenic exosomes. We have also previously confirmed that the up-regulation of mTOR is an important mechanism of PDN, and our bioinformatics analysis combined with other studies indicate that there are binding Motifs of repressor protein Rbfox1 negatively regulating mTOR pre-mRNA alternative splicing in lncRNA-Noteg1 and can competitively bind and release its repression. Therefore, we propose that HP-infected gastrogenic exosomal lncRNA-Noteg1 promotes mTOR pre-mRNA alternative splicing and the expression of mTOR via competitive binding of Rbfox1, which is a new mechanism of hyperalgesia in PDN. In this project, we arm to verify the above scientific problems using RNA immunoprecipitation (RIP) and RNA pull-down experiment combined with overexpression and shRNA lentiviral vector transfection and electrophysiological techniques, elucidate the specific mechanism of HP infection in the pathogenesis of PDN and help identify lncRNA-Noteg1 as a novel therapeutic target for the treatment of PDN.