| Objective: To observe the effects of valproic acid on sciatic nerve axonal regeneration following axotomies in rats.Methods: 36 clean SD rats models were made after all rats' right sciatic nerve were cut and then repaired with technique of neurorrhaphy. Then all injured rats were divided randomly into 3 groups and there were 12 rats in each group. All rats divided into the valproic acid group were treated with valproic acid (group A), control group I with natriicholoride (group B), vitamin group with Vitamin B1 & B6 capsule (group C). After 4, 8 and 12 weeks, 4 rats at the same time were picked out randomly from each group and their Sciatic nerve Function Index (SFI), Nerve Conduct Velocity (NCV) and sciatic Nerve Axon Counting (NAC) were measured and compared with each other.Histomorphometry, Electromyographic and Image analysis were determined at 4, 8 and 12weeks post operation.Results: (1) general view: The psychosis and appetite of rats in group B were worse than group A and C, and lost weight, moved slowly. The right hindlimb of 5 rats in control group had developed a change of swelling, ulcer formation and lose of toes at 2 weeks post operation, not healing at 12 weeks post operation. While only 2 in group A showed the same symptom at 2 weeks after operation, and healing at 12 weeks post operation. There were severe conglutination and cicatricial tissue in the lesion of sciatic nerve in group B and C. The hindlimb of all groups atrophied to some extent. (2)The sciatic nerve function index of valproic acid group (-74.75±1.55, -67.41±2.21, -55.29±0.82) is better than control group (-84.60±2.00, -79.43±0.72, -73.41 ±0.94) and Vitamin Bl & B6 group (-77.15±0.90, -73.55±0.92, -63.48±0.57), (/?<0.05). (3) The regenerated nerve motion evoked potential of valproic acid group (2.19±0.13, 1.97±0.28, 1.6U0.73) is btter than control group (3.10tb2.1I, 2.62±1.79, 2.58±0.16) and Vitamin Bl & B6 group (2.64±1.94, 2.59±0.67, 2.54±0.09), (P<0.05). (4) phosphotungstic acid-hematoxylin staining: regenerating nerve were arranged in bundles in group A, there were a large amount of regenerative collagen fibers between fasciculus and no cicatricial tissue. While the nerve fibers in group B and C spread randomly. (5) The average number of myelinated nerve fibers per area in valproic acid group (152.33±7.88) is more than that in control group (116.08±12.63) and Vitamin Bl & B6 group (136.42±11.41), (P<0.05). And the diameter of myelinated nerve fibers were 3.88±0.68um (group A), 3.69±1.02um (group B), 3.72±0.86um (group C) (p>0.05)respectively in there groups, while the difference between two group had no significance. (6) Electron microscopy show a large number of myelinated and unmyelinated fiber arranged in buddies. The regenerative sprouting of fibers were surrounded by Schwann cell, thick myelinated axons were found.Conclusion: The results demonstrate that valproic acid is able to enhance sciatic nerve regeneration and recovery of motor ruction in adult rats, suggesting the potential clinical application of valproic acid for the treatment of peripheral nerve injury in humans. |
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