| [Objective]:To investigate the feasibility of Cholecystokinin-octapeptide (CCK-8) on promoting the regeneration of peripheral nerves as well as its possible mechanism,after confirmed that CCK-8 can promote the peripheral nervous system damage repair and the regeneration, anticipated for seeks the peripheral nerve treatment medicine to provide a new mentality. [Methods] :48 SD rats were randomly divided into two groups:Test group (CCK-8-treated group ) and control group ( physiological saline-treated group ).with 24 in each.The right sciatic nerve was transected and sutured epineurium immediately .CCK-8 groups were injected with CCK-8(8nmol/kg) intraperitoneally one time per day,7 days total. And control groups received isotonic saline of the same volume. At 1 week interval after surgery,the sciatic nerve stump irmnediately distal to the injured site was harvested.Immunohistochemistry and image analysis were done to evaluate the expression of NGF protein. After operation , each group was randomly further divided into two groups which according to the observing periods for 4 and 12 weeks respectively.Denervated changes of rat and morphologic changes of regenerated nerve were observed and recovery rate of sciatic function index ( SFI % ) was measured to observe the function restoration of damaged hind limbs.Recovery rate of the complex muscular action potential ( CMAP % ) and motor nerve conduction velocities (MNCV%) were measured with Nerve-Electrophysiological instrument.Specimens in the distal ends of regenerated nerves were sectioned histologically and stained with hematoxylin and eosin,Firmly green myelinic membrane dyeing to observe the histomophologic changes under light microscope.Then, quantitative analysis of recovery rate of myelinated fiber populations were performed.Electron microscope was used to observe the ultrastructure changes.The recovery rate of wet weight of gastrocnemius muscle measured to observe the effect of CCK-8 on atrophy of skeletal muscles.[Results]:All the 48 enrolled rats was involved in the result analysis.(1)The dyeing density of NGF protein expression of CCK-8 treated group are 131.42±24.87.that of control group are 94.91±19.64.The dyeing area of NGF protein expression of CCK-8 treated group are 80.78±5.96.that of control group are 57.30±6.06.there were difference statistically between two groups.(2) General morphology:At 12 weeks the sciatic nerve of CCK-8 group is thicker than that of control group.(3) The recovery rate of SFI showed that:-60.97±10.11% in CCK-8 group and -73.67±8.86% in control group at 4 weeks;-31.06±14.38% in CCK-8 group and -41.95±8.67% in control group at 12 weeks.The difference between two groups were all significant statistically.(4) Result of Nerve-electrophysiology:at 4 weeks MNCV% and CMAP% of CCK-8 group are 26.65±4.68% and 30.22±9.63%, that of control group are 26.65±4.68% and 30.22±9.63%, there were difference statistically between two groups.At 12 weeks , MNCV% and CMAP% of CCK-8 group are 58.20±5.58% and 81.61±9.10 %,that of control group are 43.00±6.91% and 62.77±11.77%,there were difference statistically between two groups.(5)The observation of light microscope and electronmicroscope:at 4 weeks,the regenerated fibers in CCK-8 group were denser and more regular than that in control group,At 12 weeks,the fibers in CCK-8 group were more regular and homogeneous and the myelin sheaths were thicker than that in control group.The observation was further confirmed under electron microscopy.(6).Quantitative analysis of the recovery rate of myelinated fiber population: at 4 weeks in CCK-8 group: 50.31±3.50%,in control group:38.13±6.28%; at 12 weeks,in CCK-8 group: 81.63±3.94%, in control goup:60.15±7.38%.The difference between two goups were all significant statistically.(7)The recovery rate of wet weight of gastrocnemius muscle:at 4 weeks,in CCK-8 group:77.59±5.12%,in control group: 67.61±5.28%; at 12 Weeks,in group CCK-8:88.04±6.63%,in control goup:76.19±6.33%.The difference between two groups were all significant statistically.[Conclusions]:1.Cholecystokinin-octapeptide can improve the functional rehabilitation of iniured peripheral nerves through the mechanisms such as increasing the level of endogenous NGF protein.2.The administration of Cholecystokinin-octapeptide can effectively promotes the regeneration of peripheral nerves.After administrating Cholecystokinin-octapeptide,the quantity and quality of regenerating nerves are superior to control groups,moreover,the restoration of conduction velocityes of regenerating nerve fibers and the limb functions have been improved too.Cholecystokinin-octapeptide can prevents atrophy of skeletal muscles effectively after nerve injury.3.This study provides an experimental evidence for clinical administrating Cholecystokinin -octapeptide to promote the regeneration of peripheral nerves.
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