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ERK2 small interfering RNAs prevent epidural fibrosis via the efficient inhibition of collagen expression and inflammation in laminectomy rats
Authors:Chao Zhang  Xiaohong Kong  Chang Liu  Zhipin Liang  Huabing Zhao  Wei Tong  Guangzhi Ning  Wenyuan Shen  Liwei Yao  Shiqing Feng
Affiliation:1. Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China;2. School of Medicine, Nankai University, Tianjin 300071, China;3. Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Logistics College of CAPF, Tianjin 300309, China
Abstract:Laminectomy is a widely accepted treatment for lumbar disorders. Epidural Fibrosis (EF) is a common post-laminectomy or post-discectomy complication, which is thought to cause recurrent pain. RNA interference (RNAi) is a process by which double-stranded RNA triggers the destruction of mRNAs sharing the same sequence. Previously, extra-cellular signal-regulated kinase (ERK) 2 plays crucial roles in suppressing the collagen expression. To investigate the effects of lentiviral ERK2 siRNA on the prevention of post-laminectomy EF formation in a rat model, a controlled double-blinded study was conducted in 75 healthy adult Wistar rats that underwent laminectomy. They were divided randomly into 3 groups according to the treatment method: (1) control group; (2) ERK scrRNA group; (3) ERK siRNA group. All rats were euthanized humanely 4 weeks post-laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density and inflammatory factors expressions were performed. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density and inflammatory factors expressions all suggested better results in ERK siRNA group than other two groups. None of the rats expired and no obvious adverse effects were observed. Local delivery of a lentiviral siRNA targeting ERK2 can prevent epidural scar adhesion in post-laminectomy rat via inhibiting collagen expression and inflammation.
Keywords:FBSS, failed back surgery syndrome   EF, epidural fibrosis   RNAi, RNA interference   ERK2, extra-cellular signal-regulated kinase 2   siRNAs, small interfering RNAs   TGF-β1, transforming growth factor-β1   IL6, interleukin 6   GFP, green fluorescent protein   DMEM, Dulbecco&rsquo  s Modified Eagle&rsquo  s Medium   SEPs, sensory-evoked potentials   BBB locomotion test, Basso, Beattie, and Bresnahan locomotion test   HPC, hydroxyproline content
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