摘要
背景:脊髓损伤(SCI)是一种严重的疾病,可使患者导致不良后果。基因治疗作为一种有效的治疗策略已被用于治疗多种疾病.。但对脊髓损伤的治疗效果也有待实践。 目的:在这里,我们探讨神经生长因子效应管理在脊髓损伤由单纯疱疹病毒(HSV)携带的影响。 方法:含转基因重组人神经生长因子是利用构建的质粒包围中,然后删除有ICP27,ICP4和ICP34.5基因的非复制单纯疱疹病毒载体。接下来,单纯疱疹病毒重组携带神经生长因子注入脑脊液中,通过BBB评分结果检测腰椎脊髓神经生长因子对运动功能的改善。同时,IHC,qPCR和WB来证实神经生长因子转导。 结果:SCT后,BBB评分明显下降,随后随着时间的推移逐步限制恢复。荧光定量PCR证实与假手术组比较,神经生长因子 mRNA的表达在脊髓在术后28天升高,说明内源性神经生长因子能修复运动功能的限制。此外,单纯疱疹病毒携带神经生长因子注入脊髓蛛网膜下腔,结果在后肢从7dpo到49dpo有一个明显的功能改善。神经生长因子在单纯疱疹病毒携带神经生长因子给药组水平明显只高于空载体组和SCT组。 结论:我们的研究结果表明,单纯疱疹病毒携带神经生长因子在蛛网膜下腔重组释放,可有效地改善受SCT大鼠后肢的运动功能,支持单纯疱疹病毒携带神经生长因子策略可用于在未来的临床实践治疗脊髓损伤。
关键词: 单纯疱疹病毒,脊髓损伤,神经生长因子,SCT,蛛网膜下腔,运动功能。
Current Gene Therapy
Title:Releasing of Herpes Simplex Virus Carrying NGF in Subarachnoid Space Promotes the Functional Repair in Spinal Cord Injured Rats
Volume: 16 Issue: 4
Author(s): Zhi-Wei Chen, Hang-Ping Wang, Feng-Mei Yuan, Xiao Zhang, Xiu-Juan Dong, Rui-Shen Xie, Chao Tian, Bing-Shen Li, Zhen-Wu Sun and Long-Hui Zhou, Jian Liu, Ting-Hua Wang
Affiliation:
关键词: 单纯疱疹病毒,脊髓损伤,神经生长因子,SCT,蛛网膜下腔,运动功能。
摘要: Background: Spinal cord injury (SCI) is a serious disease which can lead to bad consequence in patients. Gene therapies, as an effective strategy, have been developed for the treatment of several diseases. But the effect for the treatment of SCI is also waiting to be practiced.
Objective: Here, we explored the effect of NGF administration carried by herpes simplex virus (HSV) in the injured spinal cord. Methods: Transgenic recombinant containing human NGF was constructed by using pSP72 plasmid, then enveloped by non-replication HSV vector with deleted ICP27, ICP4 and ICP34.5 genes. Next, HSV recombinant carrying NGF was injected into cerebrospinal fluid in the lumbar cord to detect the effect of NGF for the improvement of motor function, indicated by BBB score. Meanwhile, IHC, QPCR and WB were used to confirm the NGF transduction. Results: After SCT, BBB score was largely decreased, followed by a gradual limit recovery with time going on. Q-PCR confirmed that the mRNA expression of NGF was increased in the spinal cord at 28 days post-operation, compared with that in the sham group, which suggests endogenous NGF may be available to the limit repair of motor function. Moreover, HSV carried NGF was injected into subarachnoid space of the spinal cord, which results in a significant functional improvement in hindlimbs from 7dpo to 49dpo. The level of NGF in HSV-NGF administrated group was obviously higher than that in the empty vector group and SCT group, only. Conclusion: Our results demonstrate that releasing of HSV-NGF-recombinant in subarachnoid space, can effectively improve the motor function in hindlimbs of rats subjected to SCT, which supports that strategy of HSV carrying NGF may be used for the treatment of SCI in future clinic practice.Export Options
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Cite this article as:
Zhi-Wei Chen, Hang-Ping Wang, Feng-Mei Yuan, Xiao Zhang, Xiu-Juan Dong, Rui-Shen Xie, Chao Tian, Bing-Shen Li, Zhen-Wu Sun and Long-Hui Zhou, Jian Liu, Ting-Hua Wang , Releasing of Herpes Simplex Virus Carrying NGF in Subarachnoid Space Promotes the Functional Repair in Spinal Cord Injured Rats, Current Gene Therapy 2016; 16 (4) . https://dx.doi.org/10.2174/1566523217666161121105717
DOI https://dx.doi.org/10.2174/1566523217666161121105717 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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