Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats.
Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats.
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DOI：
10.1016/j.juro.2010.04.066
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发表时间：
2010-09
期刊：
影响因子：
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通讯作者：
Yoshimura N
中科院分区：
文献类型：
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作者：
Miyazato M;Sugaya K;Saito S;Chancellor MB;Goins WF;Goss JR;de Groat WC;Glorioso JC;Yoshimura N
我们研究了是否复制缺陷型单纯疱疹病毒（HSV）载体编码基因的谷氨酸脱羧酶（GAD），γ-氨基丁酸合成酶，可以抑制逼尿肌括约肌协同失调（DSD）大鼠脊髓损伤（SCI）。脊髓化后一周，将表达GAD和绿色荧光蛋白的HSV载体（HSV-GAD）注射到膀胱壁。未注射HSV的SCI大鼠（假手术）和注射编码LacZ的HSV载体（HSV-LacZ）的SCI大鼠用作对照。病毒注射后3周，在清醒状态下对3组患者同时记录尿道压力和膀胱内压力。在HSV-GAD组中，膀胱收缩期间的尿道压力升高与sham或HSV-LacZ组相比显著降低77-79%，但膀胱活动和尿道基线压力在三组之间没有差异。鞘内应用荷包牡丹碱，GABAA拮抗剂，几乎完全逆转膀胱收缩时尿道压力升高的下降，而鞘内应用saclofen，GABAB拮抗剂，部分逆转it. In HSV-GAD组，GAD 67 mRNA在L 6-S1背根神经节，膀胱传入神经的起源，与HSV-LacZ组相比，显着增加。以HSV为载体的GAD基因转移到膀胱传入通路可能是治疗脊髓损伤后DSD的一种新方法。
We investigated whether replication-defective herpes simplex virus (HSV) vectors encoding genes of glutamic acid decarboxylase (GAD), the gamma-aminobutyric acid synthesis enzyme, can suppress detrusor-sphincter dyssynergia (DSD) in rats with spinal cord injury (SCI). One week after spinalization, HSV vectors expressing GAD and green fluorescent protein (HSV-GAD) were injected to the bladder wall. SCI rats without HSV injection (sham) and those injected with LacZ-encoding HSV vectors (HSV-LacZ) were used as controls. Three weeks after viral injection, simultaneous recordings of urethral pressure and intravesical pressure were performed under an awake condition in three groups. In the HSV-GAD group, the urethral pressure rise during bladder contractions was significantly reduced by 77–79% compared with sham or HSV-LacZ groups, but bladder activity and urethral baseline pressure were not different among three groups. Intrathecal application of bicuculline, a GABAA antagonist, almost completely reversed the decrease in urethral pressure rise during bladder contractions whereas intrathecal saclofen, a GABAB antagonist, partially reversed it. In the HSV-GAD group, GAD67 mRNA was significantly increased in L6-S1 dorsal root ganglia, where bladder afferents originate, compared with the HSV-LacZ group. HSV-based GAD gene transfer to bladder afferent pathway may represent a novel approach for the treatment of DSD in SCI.
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6.6
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