中文摘要
慢性痒不仅是皮肤疾病的主要症状,也在某些系统性疾病中发生,严重降低患者的生活质量。电针疗法治疗慢性痒临床疗效确切,但其神经生物学机制不清,尚未筛选出最佳治疗方案,严重阻碍了电针止痒在临床上的推广应用。脊髓背角痒特异性受体GRPR的发现,为研究电针止痒的神经生物学机制提供了新的契机。在前期研究中我们发现,内源性大麻素参与电针对脊髓背角强啡肽和痒特异性受体GRPR的良性双向调节作用。本项目在此基础上,首先筛选出电针改善慢性痒和痒特异性受体GRPR表达的最佳治疗方案,解决慢性痒反复发作、迁延不愈的临床难题,然后采用高效液相色谱和质谱联用、免疫荧光双标、分子生物学、微透析、ELISA等技术,和两种大麻受体、GRPR神经元上κ阿片受体基因条件性敲除小鼠,深入研究内源性大麻素系统参与电针抑制慢性痒和痒特异性受体GRPR表达的神经生物学机制,为电针治疗慢性痒的临床应用提供新的理论依据和治疗策略。
英文摘要
Chronic itch is not only a symptom of skin disease, but also frequently subsequent to some systemic diseases, and reduces the living quality of the patients severely. Therapeutic effect of electroacupuncture (EA) treatment to chronic itch is exactly, but the neurobiological mechanisms of EA inhibiting chronic itch is not clear. Up to now, the best therapeutic regimen of EA for chronic itch has not been selected, and it seriously hinders the clinical applications of EA inhibiting chronic itch. The discovery of Gastrin-releasing peptide receptor (GRPR) which is specific for itch in spinal cord dorsal horn provides a new opportunity for the study of the neurobiological mechanisms of EA treatment on chronic itch. In our preliminary study, we found that endocannabinoids are involved in bidirectional benign regulation of EA on dynorphin (DYN) and specific receptor of itch (GRPR) in spinal cord dorsal horn. On this basis, we will firstly screen out the best therapy regimen of EA alleviating chronic itch and decreasing GRPR expression, in order to solve the intractable clinical problem of chronic itch. Then, using high performance liquid chromatography and mass spectrometry (HPLC-MS), double-labelling immunofluorescence, microdialysis, ELISA and molecular biology technology, and mice with conditional knockout cannabinoid receptors and κ opioid receptor on GRPR neurons, we will carry out intensive study about the neurobiological mechanisms of EA relieving chronic itch and decreasing GRPR expression by endocannabinoids. Our study will provide a new theoretical basis and therapeutic strategies for clinical applications of EA treating chronic itch.
