Effects of Herpes Simplex Virus Vector-Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception
Effects of Herpes Simplex Virus Vector-Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception
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DOI：
10.1089/hum.2011.180
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发表时间：
2013-02-01
影响因子：
4.2
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
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作者：
Yokoyama, Hitoshi;Oguchi, Tomohiko;Yoshimura, Naoki
我们之前报道了单纯疱疹病毒（HSV）载体介导的脑啡肽对膀胱过度活动和疼痛的影响。在这项研究中，我们评估了vHPPE（E1 G6-ENK），一个新的工程复制缺陷型HSV载体编码人前脑啡肽原（hPPE）的影响。在以下研究之前2周，将vHPPE或对照载体注射到雌性大鼠的膀胱壁中。逆转录PCR研究显示，在vHPPE组中，支配膀胱的L 6背根神经节中hPPE转基因水平较高。与对照组相比，vHPPE组的冻结行为（与膀胱疼痛相关的伤害性反应）的数量也显著降低。与对照载体注射组相比，vHPPE组膀胱注射树脂毒素（RTx）后L 6脊髓c-fos阳性细胞数和尿白细胞介素（IL）-1 β和IL-6水平显著降低。在连续膀胱测压中，vHPPE组显示在膀胱中施用RTx后收缩间期减少较小。盐酸纳洛酮可拮抗这种镇痛作用。因此，编码hPPE的HSV载体vHPPE证明了由膀胱刺激诱导的内脏疼痛的生理改善。基因治疗可能是一个潜在的有用的治疗方式膀胱过敏性疾病，如膀胱疼痛综合征/间质性膀胱炎。
We previously reported the effects of herpes simplex virus (HSV) vector-mediated enkephalin on bladder overactivity and pain. In this study, we evaluated the effects of vHPPE (E1G6-ENK), a newly engineered replication-deficient HSV vector encoding human preproenkephalin (hPPE). vHPPE or control vector was injected into the bladder wall of female rats 2 weeks prior to the following studies. A reverse-transcription PCR study showed high hPPE transgene levels in L6 dorsal root ganglia innervating the bladder in the vHPPE group. The number of freezing behaviors, which is a nociceptive reaction associated with bladder pain, was also significantly lower in the vHPPE group compared with the control group. The number of L6 spinal cord c-fos-positive cells and the urinary interleukin (IL)-1 beta and IL-6 levels after resiniferatoxin (RTx) administration into the bladder of the vHPPE group were significantly lower compared with those of the control vector-injected group. In continuous cystometry, the vHPPE group showed a smaller reduction in intercontraction interval after RTx administration into the bladder. This antinociceptive effect was antagonized by naloxone hydrochloride. Thus, the HSV vector vHPPE encoding hPPE demonstrated physiological improvement in visceral pain induced by bladder irritation. Gene therapy may represent a potentially useful treatment modality for bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.