Protective effects of Niacinamide against axial loading induced degeneration of rabbit lumbar disc / 中国组织工程研究

ABSTRACT

BACKGROUND:Recent studies have demonstrated that Niacinamide is capable of promoting the proliferation of intervertebral cells and improving intervertebral disc degeneration.Overloading is thought to the main cause of intervertebral disc degeneration.However,the protective effects of Niacinamide in loading induced intervertebral disc degeneration remains uncertain,OBJECTIVE:To investigate the protective effects of Niacinamide against axial loading induced degeneration of rabbit lumbar disc.DESIGN,TIME AND SETTING:A randomized controlled experiment was carded out in the Central Laboratory and the Laboratory of Department of Orthopaedics,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from November 2008 to April 2009.MATERIALSTwenty-four Japanese white rabbits (4 months old,weighing 2.0 kg).Niacinamide was supplied by Tianjin Damao Chemical Reagent Factory.METHODS:Twenty-four Japanese white rabbits were randomly divided into 6 groups.The controllable axial loading induced rabbit lumbar disc degeneration model was adopted to impose 98N pressure on the rabbit discs to induce degeneration.Various doses of Niacinamide were given intragastrically to the rabbits in different groups2 rabbits in group 1,the loading device was installed without pressing,and no Niacinamide was given;2 rabbits in group 2,given 50 mg/kg Niacinamide for 1 week;5 rabbits in group 3,loaded with 98N for 1 week;5 rabbits in group 4,loaded with 98N for 1 week,then the pressure was released for another week's recovery;5 rabbits in group 5,loaded with 98N and given 50 mg/kg Niacinamide for 1 week;5 rabbits in group 6,loaded with 98N for 1 week and then the pressure was released for another week's recovery,50 mg/kg Niacinamide was continually given during the 2 weeks.MAIN OUTCOME MEASURES:Magnetic resonance image and Thompson's grading system were used to assess degeneration degree of the discs;hematoxylin and eosin staining,immunohistochemical staining for type Ⅱ collagen,and Safranin O staining were used to evaluate histological changes;immunohistochemical staining for P161NK4A was used to evaluate cell proliferation and senescence.RESULTS：①According to the Thompson's grading system，there was no disc exhibited degeneration in group 2；5 rabbits graded Ⅱ in group 3；4 rabbits graded Ⅱ and 1 rabbit graded Ⅲ in group 4；2 rabbits graded Ⅰ and 3 rabbits graded Ⅱ in group 5；3 rabbits graded Ⅰ and 2 rabbits graded Ⅱ in group 6.MRI results revealed the alleviated degeneration in Niacinamide given groups.②The content of type Ⅱ collagen of annulus fibrosus of group 6 was 53.2% higher than that of group 4 (P＜0.01).③Safranin O-Fast Green staining density of group 2 was higher than that of group 1；The staining density of nucleus pulposus and annulus fibrosus of groups 5 and 6 was higher than the corresponding parts of group 4，especially that of nucleus pulposus (P＜0.01，P＜0.01)，and group 6 exhibited slightly increased levels than group 5.④P16INK4A positive staining rates decreased with the extension of Niacinamide administration time.CONCLUSION：Niacinamide can help to alleviate overloading-caused damage to intervertebral disc，and can benefit the recovery of damaged intervertebral disc.