期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 170, 期 4, 页码 796-806出版社
WILEY
DOI: 10.1111/bph.12301
关键词
resveratrol; spinal cord injury; sublesional bone loss; oxidative stress; inflammation; PPAR gamma; Wnt/beta-catenin; IGF-1
Background and PurposeSublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of the present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal cord-injured rats. Experimental ApproachComplete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400mgkg(-1) body mass per day(-1), intragastrically) was initiated 12h after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI. Key ResultsTreatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral total sulfhydryl content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the up-regulation of mRNA levels of PPAR, adipose-specific fatty-acid-binding protein and lipoprotein lipase, and restored mRNA levels of Wnt1, low-density lipoprotein-related protein 5, Axin2, ctnnb1, insulin-like growth factor 1 (IGF-1) and receptor for IGF-1 in femurs and tibiae. Conclusions and ImplicationsTreatment with RES attenuated sublesional bone loss in spinal-cord-injured rats, associated with abating oxidative stress, attenuating inflammation, depressing PPAR signalling, and restoring Wnt/-catenin and IGF-1 signalling.
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