LIPUS通过施旺细胞外泌体源性miRNA-21-5p修复海绵体神经改善勃起功能的机制研究

根治性前列腺切除术后因海绵体神经（CN）损伤而引起的勃起功能障碍（ED）是临床治疗难点。低强度脉冲超声(LIPUS)因其促进组织愈合、修复神经的作用被认为是神经损伤性ED的潜在治疗方法。课题组前期发现LIPUS能明显改善CN损伤大鼠ED模型的勃起功能，进一步的研究证实了适当能量的LIPUS能促进施旺细胞（SCs）增殖并刺激其分泌大量的外泌体（Exo），LIPUS-SCs-Exo可显著促进CN轴突生长。经外泌体测序分析和实验验证，提示LIPUS-SCs-Exo源性miRNA-21-5p是促进神经再生的关键效应因子，但具体分子机制尚不清楚。因此本项目在前期研究基础上结合生信分析，拟从分子、细胞及动物水平验证miRNA-21-5p靶向SPRY2调控Akt/CREB通路，抑制神经细胞凋亡和促进神经再生，以期阐明LIPUS促进神经再生改善勃起功能的内在机制，为神经损伤性ED的研究提供原创性成果。

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) after radical prostatectomy (RP), is a big clinical challenge. Low-intensity pulsed ultrasound (LIPUS) has been considered as a potential treatment for neurogenic ED due to its role in promoting tissue healing and nerve regeneration. Our team has found that LIPUS can improve the erectile function in the rat model of CNI. Further studies have confirmed that LIPUS at appropriate energy level can promote the proliferation of Schwann cells (SCs) and stimulate their secretion of exosomes. Furthermore, the exosomes can promote the outgrowth of the nerve axons. Exosomes sequencing analysis and experimental verification suggested that miRNA-21-5p derived from LIPUS-SCs-Exo is a key effector of nerve regeneration, but the mechanism is still unclear. Therefore, this project intends to reveal the role of miRNA-21-5p/SPRY2 interaction in regulating Akt/CREB pathway, inhibiting neuron apoptosis and promoting nerve regeneration at the molecular, cellular and animal levels. Hopefully, we will elucidate the mechanism of LIPUS promoting nerve regeneration and improving erectile function, and provide new insights in the field of nerve injury ED.