生殖股神经生殖支移位海绵体神经修复大鼠神经源性勃起功能障碍的研究

Neurologic disorders resulted from spine fracture of lumbar 1 and congenital tethered cord syndrome often cause degeneration and necrosis of the medullary cone, and the prevalence of erectile dysfunction in those patients was up to 75%. However, the current treatment has limited efficacy. Our previous study showed that erectile function could restore by neural anastomosis between the proximal stump of genital branch of genitofemoral nerve and the distal stump of cavernous nerve in male rats, called nerve rerouting. Three months post anastomosis, electrostimulation of genital branch resulted in a significant increase of intracavernosal pressure, and automatic copulatory behavior and fertility were regained in some rats. Therefore, we presumed that a new reflex arc might be established successfully after nerve rerouting. The new erection reflex pathway may be as following: receptor (the inguinal skin) → afferent nerve (femoral branch of genitofemoral nerve) → spinal cord (L1-2) →efferent nerve (genital branch of genitofemoral nerve-regenerative nerve) →effector (penis). In our present study, using a series of methods, including neural tracing, immunofluorescence, ELISA and electrophysiology, we intend to confirm the reconstruction of erection reflex arc, identify the release of neurotransmitter and its effective mechanism as well as investigate the restoration of erectile function, sexual behavior and fertility. In conclusion, this study will provide new theoretical evidence and technique innovation for the treatment of neurogenic erectile dysfunction.

脊柱骨折（多发于腰1）和先天性脊髓栓系可直接导致脊髓圆锥神经元变性坏死，这些患者勃起功能障碍发生率高达75%，目前治疗效果不佳。我们的前期研究显示，将雄性大鼠生殖股神经生殖支近心端与海绵体神经远心端吻合（称为神经移位术），三个月后电刺激生殖支可引起海绵体内压显著升高，且部分大鼠恢复自主性交能力和生育能力。因此，我们推测，神经移位后可能形成了新的勃起反射通路：感受器（腹股沟区皮肤）→传入神经（生殖股神经股支）→脊髓（L1-2）中枢→传出神经（生殖股神经生殖支-再生神经）→效应器（阴茎海绵体)。本项目拟利用神经追踪、免疫荧光、酶联免疫技术、神经超微结构观察、神经电生理等技术明确新反射通路的建立及神经递质的构成，并评估神经移位对大鼠阴茎勃起、性活动、生育能力的修复作用。此研究将为治疗神经源性勃起功能障碍提供新的理论依据。

脊柱骨折和先天性脊髓栓系等可直接导致脊髓圆锥神经元变性坏死，这些患者勃起功能障碍发生率高达75%，然而对于此类低位脊髓损伤导致的神经源性勃起功能障碍，目前尚无有效的治疗措施。神经移位术被广泛应用于重建神经反射通路，修复靶器官的功能。本课题将雄性SD大鼠生殖股神经生殖支近端与切断的海绵体神经远端行端端吻合，即通过外周神经移位使高位功能正常的脊髓中枢代替受损的骶副交感中枢，再生神经重新支配阴茎海绵体，从而形成新的勃起反射通路。我们利用神经追踪、酶联免疫技术、神经超微结构观察、神经电生理等技术方法明确新反射通路的建立及神经递质的构成，并评估神经移位对大鼠阴茎勃起、性活动等修复作用。. 研究结果表明生殖股神经生殖支移位海绵体神经后生殖股神经生殖支可以再生并长入阴茎海绵体内，神经移位后可能形成了新的勃起反射通路：感受器（腹股沟区皮肤）→传入神经（生殖股神经股支）→脊髓（L1-2）中枢→传出神经（生殖股神经生殖支-再生神经）→效应器（阴茎海绵体)。相比于损伤组，神经移位组部分大鼠可恢复自主性行为，电刺激大鼠生殖股神经生殖支可引起阴茎海绵体内压明显升高，神经逆行追踪后L1-2脊髓前角可见荧光金FG标记神经元，在阴茎海绵体内可见大量NOS阳性的再生神经纤维，海绵体组织的纤维化明显减轻。本项目的科学意义在于，从神经形态学、神经电生理学、动物行为学证实了生殖股神经生殖支移位海绵体神经可以有效修复阴茎勃起功能，为临床治疗低位脊髓损伤或先天性脊柱裂所导致的勃起功能障碍提供了新的实验和理论依据。