| ObjectiveFK506is known as an immunosupressant, with significant promoting effect forneuroregeneration. However, its application in repairing periphery nerve injury islimited because of its immunosuppressive function. Whether FK1706, the derivants ofFK506by removing the immunosuppressive structure, can have a positive impact onneuroregeneration has not been clearly established. Based on rats models of sciaticnerve injury treated with autologous nerve transplantation or bypass grafting, thisstudy attempts to investigate the neuroregenerative effects of administration ofFK1706postoperatively. Our research can be divided into2parts.Part I Experimental Study on Effects of FK1706to AccelerateNeuroegeneration after nerve transplantation sugeryObjectiveTo investigate the effects of FK1706to Neuroegeneration after nerve transplantation.Method20SD male rats,250~300g, were randomly divided into experimental (FK1706) andcontrol group. Surgery of the two groups were performed under anesthesia. Exposingleft sciatic nerve,8mm of sciatic nerve was neatly resected with a blade at0.5cmbelow the piriformis muscle.10mm of left radial nerve was harvested, thentransferred to the broken end of the sciatic nerve with end-to-end neurorrhaphy. After the operations, FK1706(0.32mg/kg) was local intramuscular injected in the left lowerlimb once daily for8weeks in the experimental group. While the control groupreceive no intervention but routine feed. Electrophysiological studies of left sciaticnerve were detected, the regenerated myelinated nerve fiber cross section area andnumber of left sciatic nerve fiber were observed, the wet muscle weight and the fibercross sectional area in left gastrocnemius muscle were measured, respectively, at8weeks after operation.Result1.The compound motor action potential (CMAP) amplitude was7.34±1.22mV in theexperimental group, and6.07±1.18mV in the control group, with significantdifferences (P<0.05). The motor nerve conduction velocity (MNCV) was6.07±0.95m/s in the experimental group, and3.78±0.46m/s in the control group,with significant differences (P<0.01).2.In the experimental group, the number of the myelinated nerve fiber was1199.53±113.73in proximal end, and701.17±78.40in distal, the myelinated nervefiber cross section area in distal was22.53±6.52μm2. In the control group, the numberof the myelinated nerve fiber was1164.73±71.39in proximal end, and532.78±100.68in distal, the myelinated nerve fiber cross section area in distal was14.39±3.13μm2.The difference in the number of the myelinated nerve fiber of proximal between twogroups has no significant (P＞0.05). The difference in the number of the myelinatednerve fiber of distal and the myelinated nerve fiber cross section area in distalbetween two groups has statistically significant (P<0.01).3.In the experimental group, the thickness of myelin sheath (mt) of the myelinatednerve fiber was0.1523±0.0520μm, the ratio of bare axon diameter divided by thetotal fiber diameter (d/D) was0.6364±0.1199. In the control group, the thickness ofmyelin sheath (mt) of the myelinated nerve fiber was0.1017±0.0773μm, the ratio ofbare axon diameter divided by the total fiber diameter (d/D) was0.4969±0.1396. Thedifference between the experimental group and the control group were distinct(P<0.05). 4. The wet muscle weight of left gastrocnemius muscle was805.91±98.82mg in theexperimental group, and702.26±78.46mg in the control group, with significantdifferences (P<0.05). The fiber cross sectional area in left gastrocnemius muscle was323.81±34.51μm2in the experimental group, and213.68±45.77μm2in the controlgroup, with significant differences (P<0.01).ConclusionFK1706can significantly promote the motor nerve conduction velocity, improve themyelinated nerve fiber cross section area and the number of nerve fiber, increase thewet muscle weight and the fiber cross sectional area in left gastrocnemius muscle forthe experimental animals underwent autologous nerve transplantation repairingsurgery. FK1706has significant effect on neuroregeneration promotion for rats afternerve transplantation surgery.Part II Experimental Study on Effects of FK1706to AccelerateNeuroegeneration after nerve bypass grafting sugeryObjectiveTo investigate the effects of FK1706to Neuroegeneration after nerve bypass grafting.Method20SD male rats,250~300g, were randomly divided into experimental (FK1706) andcontrol group. Surgery of the two groups were performed under anesthesia. Exposingleft sciatic nerve, clamping the middle of the sciatic nerve with an microscopic needleforceps for10s, then open windows with1.5mm in diameter on the epineurium of theproximal3mm point and distal3mm point to the clamping point respectively.10mmof left radial nerve was harvested, then transferred to the windows of the sciatic nervewith end-to-side neurorrhaphy. After the operations, FK1706(0.32mg/kg) was localintramuscular injected in the left lower limb once daily for8weeks in theexperimental group. While the control group receive no intervention but routine feed.Electrophysiological studies of left sciatic nerve were detected, the regenerated myelinated nerve fiber cross section area and number of left sciatic nerve fiber wereobserved, the wet muscle weight and the fiber cross sectional area in leftgastrocnemius muscle were measured, respectively, at8weeks after operation.Result1.The compound motor action potential (CMAP) amplitude was6.69±0.89mV in theexperimental group, and5.32±0.80mV in the control group, with significantdifferences (P<0.01). The motor nerve conduction velocity (MNCV) was5.98±1.14m/s in the experimental group, and4.32±0.53m/s in the control group, withsignificant differences (P<0.01).2.In the experimental group, the number of the myelinated nerve fiber was1131.67±45.28in proximal end, and708.52±39.85in distal, the myelinated nervefiber cross section area in distal was20.68±6.95μm2. In the control group, the numberof the myelinated nerve fiber was1120.70±55.22in proximal end, and468.87±119.67in distal, the myelinated nerve fiber cross section area in distal was13.29±2.39μm2.The difference in the number of the myelinated nerve fiber of proximal between twogroups has no significant (P＞0.05). The difference in the number of the myelinatednerve fiber of distal and the myelinated nerve fiber cross section area in distalbetween two groups has statistically significant (P<0.01).3.In the experimental group, the thickness of myelin sheath (mt) of the myelinatednerve fiber was0.1566±0.0659μm, the ratio of bare axon diameter divided by thetotal fiber diameter (d/D) was0.6269±0.1094. In the control group, the thickness ofmyelin sheath (mt) of the myelinated nerve fiber was0.1022±0.0485μm, the ratio ofbare axon diameter divided by the total fiber diameter (d/D) was0.5101±0.1294. Thedifference between the experimental group and the control group were distinct(P<0.05).4. The wet muscle weight of left gastrocnemius muscle was753.54±105.91mg in theexperimental group, and598.02±65.02mg in the control group, with significantdifferences (P<0.01). The fiber cross sectional area in left gastrocnemius muscle was246.55±50.41μm2in the experimental group, and178.90±33.59μm2in the control group, with significant differences (P<0.01).ConclusionFK1706can significantly promote the motor nerve conduction velocity, improve themyelinated nerve fiber cross section area and the number of nerve fiber, increase thewet muscle weight and the fiber cross sectional area in left gastrocnemius muscle forthe experimental animals underwent autologous nerve bypass grafting surgery.FK1706has significant effect on neuroregeneration promotion for rats after nervebypass grafting surgery. |
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