| Peripheral nerve injury (PNI) is a common traumatic disease in clinic and the patient's number of this disease is gradually increasing these days. It is always a focus of surgery research on how to inhibit muscle atrophy, maintain muscle's normal function and decrease the incident of physical disability. Although the technology of surgery has been improved as well as new drugs and materials have been produced, the therapeutic efficacy of PNI is still unsatisfactory.It was discovered that ubiquitin-proteasome pathway was playing a great role in both skeletal muscle atrophy and PNI for the past few years. And MG-132, one of the proteasome inhibitor could be used to inhibit the protein degradation of myocyte without innervations and to delay the emergence of nervous axonal degeneration (Wallerian degeneration). In the study we have investigated the effect of the proteasome inhibitor MG-132 on nerve injury and denervated skeletal muscle in rats by administration in locals. The results of this experiment can be provided to repair the injury in peripheral nerve and prevent the muscle atrophy. Part One: Prosthetic effects of proteasome inhibitor MG-132 on peripheral nerve injury of ratsAIM: To investigate the prosthetic effects of proteasome inhibitor MG-132 on the peripheral nerve injury of rats.METHODS:Twelve SD rats were randomly divided into 2 groups, and each group has 6 rats. Group A was MG-132 group while Group B was PBS control group. Standard model of the sciatic nerve injury was established in right limb of each rat. 10μL MG-132 (the concentration was 20μmol/L) and 10μL PBS were given by injection into a sponge that was covered on the local of injury in 0.25cm~2 in each rat of Group A and B respectively. All rats of the two groups were separately sacrificed after the detection of the sciatic function index in 1 wk. The nerves were cut from the locals of injury and were collected from the locals to the extremity for 1cm. The numbers of myelinated fibre were counted and the collections were detected by immunohistochemistry of NF and MBP. RESULTS:The SFI and the amount of myelinated fibre of Group A and B group were (-70±6),(-79±7)and (1480±372),(968±306).There were statistic differences between Group A and B in the above indexes(P<0.05)。CONCLUSION:The proteasome inhibitor MG-132 can prevent the Wallerian degeneration of peripheral nerve and promote the recovery of function destroy.Part Two: Preventive and therapeutic effects of proteasome inhibitor MG-132 on denervated muscle atrophy of ratsAIM: To investigate the preventive and therapeutic effects of proteasome inhibitor MG-132 on the denervated muscle atrophy of rats.METHODS:Thirty-six SD rats were randomly divided into 3 groups and each group has twelve rate, Group A and B were treated with 50μL and 100μL MG-132 separately while Group C was control group. Standard model of denervated gastrocnemius muscle was established in right limb of each rat. 50μL and 100μL MG-132( the concentration was 20μmol/L ) ,100μL PBS were respectively given by intramuscular injection once per day to right gastrocnemius muscle of each rat of Group A,B and C. Six rats of the each group were separately sacrificed after the last injection of the 1st and 4th week, and the gastrocnemius was harvested for measurement of atrophy rate of muscle, total proteins of muscle , diameter and cross section area of myocyte.The blood of inferior vena cava was harvested for measurement of HC and heterophil granulocyte .RESULTS:At the 1st week postinjectively, atrophy rate of muscle, total proteins of muscle , diameter and cross section area of myocyte in Group A and B were(24.5±3.5)% and (18.2±3.3)%,(9.98±0.68)mg/mL and(10.56±0.84)mg/mL,(14.61±1.26)μm and(14.96±1.34)μm,(790.25±12.26)μm~2 and(800.28±18.98)μm~2.There were significance differences among the three groups(P<0.05), and also between Group A and B in atrophy rate of muscle(P<0.05). At the 4th week postinjectively, the above indexes were(60.2±3.7)% and(52.1±4.0)%,(7.04±0.70)mg/mL and(7.96±0.68)mg/mL,(10.63±1.04)μm and(12.16±0.98)μm,(470.48±11.14)μm~2 and(498.47±10.34)μm~2 .There were statistic differences between Group A and B and Group C(P<0.05), and also between Group A and B in the above indexes(P<0.05). At the 1st week postinjectively, HC were(131.1±2.1)g/L,(132.3±2.4)g/L in Group A and B. There were not statistic differences with C group(P>0.05). At the 4th week postinjectively, HC were(133.3±2.3)g/L,(131.0±2.1)g/L in Group A and B. There were not statistic differences with C group(P>0.05)。CONCLUSION: Denervated muscle atrophy can be partly prevented by proteasome inhibitor MG-132 in rats, and the effects rely on the dose of MG-132 in 4wk. |
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