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采用 17β-雌二醇和施万细胞联合给药靶向治疗脊髓损伤大鼠模型中的轴突变性和脱髓鞘。

Targeting axonal degeneration and demyelination using combination administration of 17β-estradiol and Schwann cells in the rat model of spinal cord injury.

机构信息

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

出版信息

J Cell Biochem. 2018 Dec;119(12):10195-10203. doi: 10.1002/jcb.27361. Epub 2018 Aug 20.

DOI:10.1002/jcb.27361
PMID:30129246
Abstract

Schwann cells (SCs) are known to be responsible for axonal ensheathing and myelination, and their transplantation is used commonly for treatment of spinal cord injury (SCI). 17β-estradiol (E2) has also reported for its protective roles in neurons in the transplanted SCs to the SCI model. In the current study, we evaluated the roles of E2 administration before SCs transplantation in targeting SCI-induced axonal degeneration and demyelination. E2 (25 µg/kg, IP) was administered to the male Wistar rats underwent contusive SCI at T10 segment. At 7 days after injury, 1 × 10 SCs were transplanted to the injury epicenter of the spinal cord. The groups were laminectomy, SCI, SCI+E2, and SCI+E2+SCs. Functional recovery was evaluated using the Basso-Bresnahan-Beattie locomotor test. Sections from spinal cord were also assessed for histoloical staining, including Luxol fast blue, Bielschowsky's silver and immunofluorescence evaluation of myelin basic protein (MBP). The SCI group showed impaired locomotion in the hind limb, increased number of cavities within spinal cord, low observable numbers of regenerating fibers, and a significant decrease in the rate of expression for MBP. These changes were counteracted in the treatment groups ( P < 0.05 vs SCI) with no significant changes among them. From the results, it may be concluded that application of E2 and SCs could be effective when axons undergo demyelination and degenerative processes, and their combination could partly provide cumulative outcomes.

摘要

许旺细胞(SCs)负责轴突的鞘内包裹和髓鞘形成,其移植常用于治疗脊髓损伤(SCI)。17β-雌二醇(E2)也被报道具有保护作用,可保护移植到 SCI 模型中的SCs 中的神经元。在本研究中,我们评估了 E2 在SCs 移植前给药在靶向 SCI 诱导的轴突变性和脱髓鞘中的作用。雄性 Wistar 大鼠在 T10 节段进行压迫性 SCI 后,给予 E2(25μg/kg,腹腔注射)。损伤后 7 天,将 1×10 的SCs 移植到脊髓损伤中心。各组分别为椎板切除术、SCI、SCI+E2 和 SCI+E2+SCs。采用 Basso-Bresnahan-Beattie 运动测试评估功能恢复情况。脊髓切片还进行了组织学染色评估,包括卢索快速蓝、Bielschowsky 银染色和髓鞘碱性蛋白(MBP)免疫荧光评估。SCI 组后肢运动功能受损,脊髓内空洞数量增加,再生纤维数量明显减少,MBP 表达率显著下降。这些变化在治疗组(与 SCI 相比,P<0.05)得到了逆转,但各组之间没有显著差异。从结果可以得出结论,E2 和SCs 的应用在轴突发生脱髓鞘和退行性过程时可能是有效的,它们的联合应用可能部分提供累积效果。

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