Effect of adenovirus-mediated RNA interference of IL-1β expression on spinal cord injury in rats

Effect of adenovirus-mediated RNA interference of IL-1β expression on spinal cord injury in rats
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DOI:
10.1038/sc.2016.20
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发表时间:
2016-10-01
期刊:
影响因子:
2.2
通讯作者:
Ke, Q-F
Ke, Q-F
中科院分区:
医学3区
文献类型:
--
作者:
Lin, W-P;Lin, J-H;Ke, Q-F

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研究设计:我们将表达白细胞介素-1 β (IL-1 β)小发夹RNA (shRNA)的腺病毒载体引入损伤脊髓,以评估IL-1 β下调在脊髓损伤(SCI)大鼠模型中的治疗潜力。目的:探讨IL-1 β下调对大鼠创伤性脊髓损伤的保护作用。单位:中华人民共和国泉州福建医科大学第二附属医院骨科。方法:构建靶向IL-1 β的腺病毒shRNA,并在脊髓损伤前7天在T12切片注射。采用BBB (Basso-Beattie-Bresnahan)评分法评定运动功能。免疫荧光、酶联免疫吸附试验、流式细胞分析和western blots也进行了检测。结果:下调IL-1 β的动物在脊髓损伤后运动功能恢复明显加快,神经元损失减少。此外,IL-1 β下调可显著降低脊髓损伤后肿瘤坏死因子- α (tnf - α)水平和Bax表达,降低caspase-3活性,升高Bcl-2表达。结论:本研究表明IL-1 β下调可能在减少创伤性脊髓损伤后继发性损伤和改善预后方面具有潜在的治疗益处。
Study design: We introduced an adenoviral vector expressing interleukin-1 beta (IL-1 beta) small-hairpin RNA (shRNA) into the injured spinal cords to evaluate the therapeutic potential of IL-1 beta downregulation in a rat model of spinal cord injury (SCI).Objectives: The purpose of this study was to investigate the possible protective effects of the IL-1 beta downregulation on traumatic SCI in rats.Setting: Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, People's Republic of China.Methods: An adenoviral shRNA targeting IL-1 beta was constructed and injected at the T12 section 7 days before SCI. The rats' motor functions were evaluated by the Basso-Beattie-Bresnahan (BBB) rating scale. Immunofluorescence, enzyme-linked immunosorbent assay, flow-cytometric analysis and western blots were also performed.Results: Animals downregulating IL-1 beta had significantly better recovery of locomotor function and less neuronal loss after SCI. In addition, IL-1 beta downregulation significantly decreased tumor necrosis factor-alpha (TNF-alpha) level and Bax expression, reduced the activity of caspase-3 and increased Bcl-2 expression after SCI.Conclusion: This study demonstrated that the IL-1 beta downregulation may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI.