【摘要】：目前已知FK506是一種免疫抑制劑，具有顯著促進(jìn)神經(jīng)再生作用，但其免疫抑制作用限制了其在周圍神經(jīng)損傷修復(fù)中的應(yīng)用。按照去除其免疫抑制結(jié)構(gòu)設(shè)計(jì)的衍生物FK1706的是否有促進(jìn)神經(jīng)再生作用，尚未明了。本研究通過建立大鼠坐骨神經(jīng)損傷神經(jīng)移植與神經(jīng)旁路移植模型，術(shù)后應(yīng)用FK1706，探討其對(duì)修復(fù)神經(jīng)的再生作用。實(shí)驗(yàn)分為以下2個(gè)部分。 第一部分神經(jīng)移植術(shù)后FK1706促進(jìn)神經(jīng)再生作用的實(shí)驗(yàn)研究 目的： 探討神經(jīng)移植后FK1706促進(jìn)神經(jīng)再生作用。 方法： SD大鼠20只，雄性，250-300g，隨機(jī)分為實(shí)驗(yàn)組（FK1706組）和對(duì)照組。兩組麻醉后，取左側(cè)橈神經(jīng)10mm備用，顯露左側(cè)坐骨神經(jīng)干，于梨狀肌下0.5cm處，用刀片整齊切除8mm長(zhǎng)的坐骨神經(jīng)，將橈神經(jīng)移植于坐骨神經(jīng)上，兩斷端分別行端端吻合。實(shí)驗(yàn)組術(shù)后當(dāng)天開始左下肢局部肌肉注射FK1706（0.32mg/kg），持續(xù)8周。對(duì)照組神經(jīng)移植術(shù)后不做干預(yù)，常規(guī)喂養(yǎng)。8周后行大鼠左坐骨神經(jīng)神經(jīng)電生理檢測(cè)、左坐骨神經(jīng)再生有髓神經(jīng)纖維數(shù)及截面積測(cè)定、左腓腸肌肌濕重及肌纖維截面積測(cè)定。 結(jié)果： 1.實(shí)驗(yàn)組復(fù)合運(yùn)動(dòng)動(dòng)作電位（CMAP）的波幅7.34±1.22mV，對(duì)照組6.07±1.18mV，相比差異有顯著性（P0.05）。實(shí)驗(yàn)組運(yùn)動(dòng)神經(jīng)傳導(dǎo)速度（MNCV）6.07±0.95m/s，對(duì)照組3.78±0.46m/s，相比差異有顯著性（P0.01）。 2.實(shí)驗(yàn)組有髓神經(jīng)纖維數(shù)近端1199.53±113.73根，遠(yuǎn)端701.17±78.40根，遠(yuǎn)端纖維截面積22.53±6.52μm2，對(duì)照組有髓神經(jīng)纖維數(shù)近端1164.73±71.39根，遠(yuǎn)端532.78±100.68根，遠(yuǎn)端纖維截面積14.39±3.13μm2，近端有髓神經(jīng)纖維數(shù)相比差異無顯著性（P＞0.05），遠(yuǎn)心端有髓神經(jīng)纖維數(shù)、遠(yuǎn)端纖維截面積相比差異有顯著性（P0.01）。 3.實(shí)驗(yàn)組再生有髓神經(jīng)纖維的髓鞘厚度（mt）0.1523±0.0520μm，再生纖維的直徑比（d/D）0.6364±0.1199，對(duì)照組再生有髓神經(jīng)纖維的髓鞘厚度（mt）0.1017±0.0773，再生纖維的直徑比（d/D）0.4969±0.1396，相比差異有顯著性（P0.05）。 4.實(shí)驗(yàn)組腓腸肌肌濕重805.91±98.82mg，對(duì)照組腓腸肌肌濕重702.26±78.46mg，相比差異有顯著性（P0.05）。實(shí)驗(yàn)組肌纖維截面積323.81±34.51μm2，對(duì)照組肌纖維截面積213.68±45.77μm2，相比差異有顯著性（P0.01）。結(jié)論：FK1706能顯著改善大鼠神經(jīng)移植術(shù)后運(yùn)動(dòng)神經(jīng)傳導(dǎo)速度，增加吻合口遠(yuǎn)端再生有髓神經(jīng)纖維數(shù)及截面積，增加患肢腓腸肌肌濕重及肌纖維截面積。FK1706具有顯著促進(jìn)大鼠神經(jīng)移植術(shù)后神經(jīng)再生作用。 第二部分神經(jīng)旁路移植術(shù)后FK1706促進(jìn)神經(jīng)再生的實(shí)驗(yàn)研究 目的： 探討神經(jīng)旁路移植后FK1706促進(jìn)神經(jīng)再生作用。方法： SD大鼠20只，雄性，250-300g，隨機(jī)分為實(shí)驗(yàn)組（FK1706組）和對(duì)照組。兩組麻醉后，取左側(cè)橈神經(jīng)10mm備用，顯露左側(cè)坐骨神經(jīng)干，用顯微鏡持針鉗鉗夾其中點(diǎn)10s，于鉗夾點(diǎn)近、遠(yuǎn)端3mm處神經(jīng)外膜上，分別開一張直徑為1.5mm的窗口，將橈神經(jīng)與兩窗口作端側(cè)吻合。實(shí)驗(yàn)組術(shù)后當(dāng)天開始左下肢局部肌肉注射FK1706（0.32mg/kg），持續(xù)8周。對(duì)照組神經(jīng)旁路移植術(shù)后不做干預(yù)，常規(guī)喂養(yǎng)。8周后行大鼠左坐骨神經(jīng)神經(jīng)電生理檢測(cè)、左坐骨神經(jīng)再生有髓神經(jīng)纖維數(shù)及截面積測(cè)定、左腓腸肌肌濕重及肌纖維截面積測(cè)定。 結(jié)果： 1.實(shí)驗(yàn)組復(fù)合運(yùn)動(dòng)動(dòng)作電位（CMAP）的波幅6.69±0.89mV，對(duì)照組5.32±0.80mV，相比差異有顯著性（P0.01）。實(shí)驗(yàn)組運(yùn)動(dòng)神經(jīng)傳導(dǎo)速度（MNCV）5.98±1.14m/s，對(duì)照組4.32±0.53m/s，相比差異有顯著性（P0.01）。 2.實(shí)驗(yàn)組有髓神經(jīng)纖維數(shù)近端1131.67±45.28根，遠(yuǎn)端708.52±39.85根，遠(yuǎn)端纖維截面積20.68±6.95μm2，對(duì)照組有髓神經(jīng)纖維數(shù)近端1020.70±55.22根，遠(yuǎn)端468.87±119.67根，遠(yuǎn)端纖維截面積13.29±2.39μm2，近端有髓神經(jīng)纖維數(shù)相比差異無顯著性（P＞0.05），，遠(yuǎn)心端有髓神經(jīng)纖維數(shù)、遠(yuǎn)端纖維截面積相比差異有顯著性（P0.01）。 3.實(shí)驗(yàn)組再生有髓神經(jīng)纖維的髓鞘厚度（mt）0.1566±0.0659μm，再生纖維的直徑比（d/D）0.6269±0.1094，對(duì)照組再生有髓神經(jīng)纖維的髓鞘厚度（mt）0.1022±0.0458，再生纖維的直徑比（d/D）0.5101±0.1294，相比差異有顯著性（P0.05）。 4.實(shí)驗(yàn)組腓腸肌肌濕重753.54±105.91mg，對(duì)照組腓腸肌肌濕重598.02±65.02mg，相比差異有顯著性（P0.01）。實(shí)驗(yàn)組（FK1706組）肌纖維截面積246.55±50.41μm2，對(duì)照組肌纖維截面積178.90±33.59μm2，相比差異有顯著性（P0.01）。 結(jié)論： FK1706能改善大鼠神經(jīng)旁路移植術(shù)后運(yùn)動(dòng)神經(jīng)傳導(dǎo)速度，增加吻合口遠(yuǎn)端再生有髓神經(jīng)纖維數(shù)及截面積、腓腸肌肌濕重及肌纖維截面積。FK1706具有促進(jìn)大鼠神經(jīng)旁路移植術(shù)后移植神經(jīng)再生的作用。
[Abstract]:It is known that FK506 is an immunosuppressive agent which can significantly promote nerve regeneration, but its immunosuppressive effect limits its application in the repair of peripheral nerve injury. The regeneration of injured nerve graft and nerve bypass graft was studied with FK1706 after operation. The experiment was divided into the following two parts.
Part one experimental study on the effect of FK1706 on nerve regeneration after nerve transplantation
Objective:
Objective to investigate the effect of FK1706 on nerve regeneration after nerve transplantation.
Method:
20 male SD rats, 250-300 g, were randomly divided into experimental group (FK1706 group) and control group. After anesthesia, the left radial nerve was reserved for 10 mm and the left sciatic nerve trunk was exposed. At 0.5 cm below the piriformis muscle, the sciatic nerve of 8 mm length was resected with a knife blade, and the radial nerve was transplanted to the sciatic nerve. End-to-end anastomosis was performed at both ends of the sciatic nerve. FK1706 (0.32 mg/kg) was injected into the left lower limb for 8 weeks. The control group received no intervention after nerve transplantation and was fed routinely for 8 weeks.
Result:
1. The amplitude of compound motor action potential (CMAP) in the experimental group was 7.34 (+ 1.22 mV) and that in the control group was 6.07 (+ 1.18 mV) with a significant difference (P 0.05). The motor nerve conduction velocity (MNCV) in the experimental group was 6.07 (+ 0.95 m/s) and that in the control group was 3.78 (+ 0.46 m/s), with a significant difference (P 0.01).
2. The number of myelinated nerve fibers in the proximal end was 1199.53+113.73 in the experimental group, 701.17+78.40 in the distal end, 22.53+6.52 micron 2 in the distal end. The number of myelinated nerve fibers in the control group was 1164.73+71.39 in the proximal end, 532.78+100.68 in the distal end, 14.39+3.13 micron 2 in the distal end. There was no significant difference in the number of myelinated nerve fibers in the proximal end (P > 0.05). There was a significant difference in the number of myelinated nerve fibers at the heart end and the distal fiber cross-sectional area (P0.01).
3. The myelin sheath thickness (mt) of regenerated myelinated nerve fibers was 0.1523 (+ 0.0520) micron in the experimental group, and the diameter ratio of regenerated nerve fibers was 0.6364 (+ 0.1199) in the control group. The myelin sheath thickness (mt) of regenerated myelinated nerve fibers was 0.1017 (+ 0.0773) in the control group, and the diameter ratio of regenerated nerve fibers was 0.4969 (+ 0.1396) in the experimental group.
4. The wet weight of gastrocnemius muscle in experimental group was 805.91 65507 The nerve conduction velocity increased the number and cross-sectional area of the regenerated myelinated nerve fibers at the distal end of the anastomotic stoma, increased the wet weight of the gastrocnemius muscle and the cross-sectional area of the muscle fibers. FK1706 significantly promoted the nerve regeneration after nerve transplantation in rats.
The second part is an experimental study of FK1706 promoting nerve regeneration after nerve bypass grafting.
Objective:
Objective: To investigate the effect of FK1706 on nerve regeneration after nerve bypass grafting.
Twenty male SD rats, 250-300 g, were randomly divided into experimental group (FK1706 group) and control group. After anesthesia, the left radial nerve was reserved for 10 mm to expose the left sciatic nerve trunk. The left sciatic nerve trunk was clamped with a microscope needle-holding forceps for 10 seconds, and a 1.5 mm diameter window was opened on the epineurium near the forceps and 3 mm distal, respectively. End-to-side anastomosis. FK1706 (0.32mg/kg) was injected into the left lower limb muscle on the day after operation for 8 weeks. No intervention was given to the control group after nerve bypass grafting. The left sciatic nerve was electrophysiologically examined, the number and cross-sectional area of myelinated nerve fibers regenerated from the left sciatic nerve were measured, and the wet weight of left gastrocnemius muscle and muscle fibers were measured. Determination of sectional area.
Result:
1. The amplitude of compound motor action potential (CMAP) in the experimental group was 6.69 (+ 0.89mV) and that in the control group was 5.32 (+ 0.80mV) with a significant difference (P 0.01). The motor nerve conduction velocity (MNCV) in the experimental group was 5.98 (+ 1.14m/s) and that in the control group was 4.32 (+ 0.53m/s), with a significant difference (P 0.01).
2. The number of myelinated nerve fibers in experimental group was 1131.67 (+ 45.28) in the proximal end, 708.52 (+ 39.85) in the distal end and 20.68 (+ 6.95) in the distal end. The number of myelinated nerve fibers in control group was 1020.70 (+ 55.22) in the proximal end, 468.87 (+ 119.67) in the distal end, 13.29 (+ 2.39) in the distal end. There was no significant difference in the number of myelinated nerve fibers in the distal end (P > 0.05). There was a significant difference in the number of myelinated nerve fibers at the end and the distal fiber cross-sectional area (P0.01).
3. The myelin sheath thickness (mt) of regenerated myelinated nerve fibers was 0.1566 (+ 0.0659) micron and the diameter ratio of regenerated nerve fibers was 0.6269 (+ 0.1094) in the experimental group and 0.1022 (+ 0.0458) in the control group. The diameter ratio of regenerated nerve fibers was 0.5101 (+ 0.1294) in the experimental group and the difference was significant (P 0.05).
4. The wet weight of gastrocnemius muscle in experimental group was 753.54+105.91 mg, while that of control group was 598.02+65.02 mg (P 0.01).
Conclusion:
FK1706 can improve motor nerve conduction velocity, increase the number and cross-sectional area of regenerated myelinated nerve fibers, wet weight of gastrocnemius muscle and cross-sectional area of muscle fibers. FK1706 can promote nerve regeneration after nerve bypass grafting in rats.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R651.3

【共引文獻(xiàn)】

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