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慢病毒载体递送短发夹 RNA 靶向 NgR1 促进损伤大鼠脊髓神经再生和运动功能恢复。

Lentiviral vector delivery of short hairpin RNA to NgR1 promotes nerve regeneration and locomotor recovery in injured rat spinal cord.

机构信息

Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Department of Translational Medicine Center Research Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

Sci Rep. 2018 Apr 3;8(1):5447. doi: 10.1038/s41598-018-23751-2.

Abstract

Nogo receptor 1 (NgR1) is a high-affinity receptor of myelin-associated inhibitors (MAIs), and suppresses neurogenesis. Lentiviral vector are commonly used to alter the expression of targeted genes. However, little is known about the potential function of lentiviral vector harboring NgR1 shRNA (LV-NgR1 shRNA) on neurogenesis in spinal cord injury (SCI). In this study, the rats were randomly divided into three groups: including the LN (LV-NgR1 shRNA injection), LC (LV-control shRNA injection) and Sham (laminectomy only). Eight weeks post-injection of LV, spinal cords were examined by histology for changes in cavity size and by immunohistochemistry for changes in expression of NgR1, cell apoptosis, astrocytes, neurons and myelination. Motor function was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor scale. Animals that received LV-NgR1 shRNA remarkably improved the motor function. These animals also showed an increase in levels of nerve fibers, synapses and myelination, a decrease in levels of lesion cavity and cell apoptosis at 8 weeks post-treatment. These findings give evidence that NgR1 may be a promising target for SCI treatment.

摘要

神经生长抑制因子受体 1(NgR1)是髓鞘相关抑制因子(MAIs)的高亲和力受体,抑制神经发生。慢病毒载体常用于改变靶向基因的表达。然而,关于携带 NgR1 shRNA 的慢病毒载体(LV-NgR1 shRNA)对脊髓损伤(SCI)中神经发生的潜在功能知之甚少。在这项研究中,大鼠被随机分为三组:包括 LN(LV-NgR1 shRNA 注射)、LC(LV-对照 shRNA 注射)和 Sham(仅椎板切除术)。LV 注射 8 周后,通过组织学检查腔大小的变化,通过免疫组织化学检查 NgR1、细胞凋亡、星形胶质细胞、神经元和髓鞘化的表达变化,评估脊髓的变化。运动功能采用 Basso、Beattie 和 Bresnahan(BBB)运动评分进行评估。接受 LV-NgR1 shRNA 治疗的动物显著改善了运动功能。这些动物在治疗后 8 周时还显示出神经纤维、突触和髓鞘化水平增加,损伤腔和细胞凋亡水平降低。这些发现为 NgR1 可能是 SCI 治疗的一个有前途的靶点提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c17/5882972/457e1455d61a/41598_2018_23751_Fig1_HTML.jpg

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