骶上脊髓病变常导致逼尿肌过度活动(Detrusor overactivity,DO)、逼尿肌-括约肌协同失调和逼尿肌纤维化,因此产生的膀胱内高压及膀胱顺应性降低等改变严重威胁脊髓病变患者上尿路功能。但目前没有抑制DO的理想方法。有证据表明，脊髓和膀胱受到有害刺激时，脊髓背根神经节神经元内兴奋性神经递质谷氨酸的含量增加，并可导致逼尿肌的过度活动，因此降低谷氨酸受体活性以期抑制DO是本研究的假说。尿喹啉酸是谷氨酸NMDA受体的非竞争性抑制剂，它是在色氨酸代谢过程中，由尿氨酸氨基转移酶不可逆性催化下生成。单纯疱疹病毒是基因治疗研究中常用的病毒载体，能沿周围神经轴突，逆行感染大鼠L6-S1背根神经节神经元。在本研究中，我们首先构建单纯疱疹病毒介导的尿氨酸氨基转移酶基因病毒载体，将该病毒载体注射入T10脊髓横断大鼠的膀胱壁内，探索单纯疱疹病毒介导的尿氨酸氨基转移酶基因治疗脊髓病变后DO的可能性与机制

Suprasacral spinal cord lesions usually lead to detrusor overactivity，detrusor - sphincter dyssynergia and detrusor fibrosis. Detrusor overactivity is closely related to unsafe bladder pressure and low bladder compliance, which seriously threats patients'upper urinary tract function, but there is no ideal way to inhibit detrusor overactivity. Evidences showed harmful stimulation to bladder or spinal cord could increase excitatory neurotransmitter of glutamate in dorsal root ganglia, which can lead to detrusor overactivity. Kynurenic acid is a noncompetitive inhibitor for one of glutamate receptor- - NMDA receptor, which is generated by irreversible catalysis of kynurenine aminotransferase in the process of tryptophan metabolism. Neurotropic herpes simplex virus is a commonly used viral vector for gene therapy research, which could infect rat L6-S1 dorsal root ganglia along peripheral nerve axons in a retrograde manner. In this study, we first construct herpes simplex virus mediated kynurenine aminotransferase gene vector, then use it to explore the possibility and mechanisms of inhibition of detrusor overactivity by bladder wall injections in rats with T10 spinal cord transection.