slc5a7基因及其表达蛋白CHT1在慢性胰腺炎内脏痛觉高敏中的作用

内脏痛觉高敏机制尚不清楚。课题组首次发现TNBS诱导的慢性胰腺炎内脏痛觉高敏大鼠背根神经节中slc5a7基因转录和表达上调，且CHT1拮抗剂能降低痛阈，而激动剂能改善内脏痛觉高敏。目前国内外尚无该基因与疼痛关系的探讨。为进一步研究CHT1在慢性胰腺炎引起的内脏痛觉高敏中的作用，本课题拟从以下层面开展研究：1、在体动物水平阐释模型组CHT1在痛觉传导通路各层面的表达水平、细胞定位及胆碱转运活性改变。2、通过体内实验阐释神经元CHT1胆碱转运活性及表达水平改变对内脏痛及小胶质细胞、神经元结构和功能的影响。3、体外实验证明小胶质细胞是否含非神经元胆碱能系统，阐释该细胞内CHT1的表达水平改变对内脏痛及小胶质细胞、神经元结构和功能的影响。4、探讨基于单纯疱疹病毒的slc5a7基因治疗对内脏痛的疗效。该课题能拓宽对slc5a7和基因治疗的认识，有助于部分阐明内脏痛的机制，为内脏痛的治疗做出贡献。

The mechanism of visceral hyperalgesia is still unclear. Our group first found that the transcription and expression of slc5a7 in the dorsal root ganglion of rats with TNBS-induced chronic pancreatitis which was characterized by visceral hyperalgesia was upregulated. Then we found that antagonists of CHT1 can reduce the pain threshold, and its agonists can relieve visceral hyperalgesia. Up to now, there is no study focused on the relationship between slc5a7 and pain. To further confirm the role of CHT1 on visceral hyperalgesia caused by chronic pancreatitis, this subject is intended to be studied from the following levels. 1, To elucidate the expression level, cell localization and choline transport activity of CHT1 at different level of pain signaling pathways in CP group. 2, To elucidate the effects of choline transport activity and expression level of neuronal CHT1 on visceral pain, structure and function of microglia and neuron. 3, To demonstrate whether microglia contains non-neuronal cholinergic systems; to investigate the influence of changes in the expression level of CHT1 on visceral pain, structure and function of microglia and neuron. 4, To investigate the efficacy of slc5a7 gene therapy based on herpes simplex virus on visceral pain. This study can broaden the understanding of slc5a7 and gene therapy, help to partially clarify the mechanism of visceral pain and make a contribution to the treatment of visceral pain.