勃起功能障碍（ED）严重影响患者及配偶的生殖和心理健康。在手术损伤、外伤或糖尿病的病理代谢中，支配阴茎海绵体的交感神经损伤后的过度代偿再生或/和副交感神经受损后的再生障碍，导致局部植物神经不均衡重塑是难治性ED的重要病理机制。我们在前期实验中发现，通过抗体封闭神经生长因子受体（NTR）-TrkA抑制交感神经过度再生有助于术后勃起功能的恢复（EU，2015）。但该治疗对损伤的副交感神经却没有作用。在此基础上我们假设：联合促进副交感神经修复可能进一步优化重度ED的治疗效果。本项目拟研究：1）TrkA和副交感神经相关的GFRα1/2及其配体在重度ED发病过程中的变化规律；2）通过条件性编辑（CRISPR/Cas9-HITI）等技术调节TrkA和GFR α1/2表达诱导植物神经重塑对重度ED的治疗效果和机制。本项目为重度勃起功能障碍的治疗提供了一个新的思路。

Refractory erectile dysfunction (ED) including postprostatectomy ED and diabetic ED, is a world-wide health problem that respond poorly to first line treatment phosphodiesterase type 5 inhibitors (PDE5i). Previous research has illustrated that nerve injury/neuropathy including sympathetic nerve over-compensation and parasympathetic nerve regeneration disorder are important pathological changes in these patients. Exploration for novel treatments based on pathological repair may have tremendous impact on ED management. Based on our experiments on cavernous injury induced ED animal model, local injection of antibody to the high-affinity neurotrophin receptor (NTR) tyrosine kinase receptor A (TrkA) to inhibit sympathetic re-innervation could restore erectile function (EU, 2015). In order to further clarify the regulation of sympathetic/parasympathetic nerve regeneration through NTR on refractory ED, this project intends to explore: 1) expression of TrkA (mainly promotes the sympathetic nerve growth) and GFRα1/2 (mainly promotes parasympathetic nerve growth) and their ligands in penile tissue during ED development; 2) effects and mechanism of sympathectomy and parasympathetic promotion by in vivo genome editing of TrkA and GFRα1/2 using CRISPR/Cas9-HITI techniques for the treatment of refractory ED. This project will help us to develope novel treatment for ED by modifying nerve regeneration.