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13 February 2015 : Animal Research  

Effects of Rapamycin on Reduction of Peridural Fibrosis: An Experimental Study

Like LuoBCD, Chifei ZhangEF, Jinmin ZhaoBEG, Qingjun WeiAG, Xiaofeng LiBE

DOI: 10.12659/MSM.893165

Med Sci Monit 2015; 21:482-488

Abstract

BACKGROUND: Peridural fibrosis (PF) is a normal complication after lumbar surgery. It is a challenge for both surgeons and patients. Rapamycin (RPM), a novel antibiotic with anti-proliferative and immunosuppressive properties, has been shown to be effective in preventing uncontrolled scar proliferation diseases. The object of the present research was to investigate the effects of RPM on inhibiting PF in vitro and in vivo.

MATERIAL AND METHODS: In vitro, the fibroblasts collected and isolated from the rat tail skin were cultured with/without RPM and cell counting was performed. In vivo, the double-blinded study was conducted in 60 healthy Wistar rats divided randomly into 3 groups: 1) RPM treatment group; 2) Vehicle treatment group; 3) Control group. Rats underwent a L1-L2 level laminectomy with a satisfactory anesthetization. Four weeks post-operatively, the Rydell score, histological analysis, hydroxyproline content, vimentin expressional level, and inflammatory cytokines expressional levels were assessed.

RESULTS: In vitro, RPM showed ability to prevent fibroblast proliferation. In vivo, the laminectomy was well tolerated by all rats, which were killed 4 weeks post-operatively. The Rydell score, histological evaluation, hydroxyproline content, vimentin expression level, and inflammatory activity showed the positive effect of RPM in preventing peridural adhesion, inhibiting fibrotic formation and collagen synthesis, and down-regulating inflammation.

CONCLUSIONS: In the present primary study, RPM showed good efficacy in preventing the proliferation of fibroblasts. RPM can prevent rat peridural adhesion through inhibiting collagen synthesis, fibroblasts proliferation, and inflammatory activity.

Keywords: Analysis of Variance, Cell Proliferation - drug effects, Cells, Cultured, Cytokines - metabolism, DNA Primers - genetics, Drug Evaluation, Preclinical, Fibroblasts - physiology, Fibrosis - prevention & control, Hydroxyproline - metabolism, Laminectomy, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Sirolimus - pharmacology, Spinal Cord - pathology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750