【摘要】 目的探讨鹿茸多肽局部给药和鹿茸多肽-PLGA复合膜对大鼠坐骨神经损伤后神经再生的影响。方法制备厚度为50μm、浓度分别为3mg/g及15mg/g的鹿茸多肽-PLGA复合膜。取3～6月龄Wistar大鼠72只,雌雄不限,体重(250±50)g,制备坐骨神经切断模型。模型制备后随机分成4组,每组18只。A组:吻合后不作任何处理;B组:术后每隔1d术侧腓肠肌内注射10mg/L鹿茸多肽1mL;C组:神经吻合口部位包绕3mg/g鹿茸多肽-PLGA复合膜;D组:神经吻合口部位包绕15mg/g鹿茸多肽-PLGA复合膜。术后第2、4及6周,大体观察神经断端粘连情况,行电生理检测、免疫组织化学染色及半定量分析、辣根过氧化物酶(horseradish peroxidase,HRP)逆行示踪。结果术后各组大鼠行为无明显异常,足底、足趾均无溃疡;神经吻合口处均无神经瘤形成。术后2、4及6周,A组神经吻合处与周围组织粘连明显,B组仅有轻度粘连,C、D组无明显粘连。术后各时间点小腿三头肌诱发电位恢复率B、C、D组明显高于A组(P<0.01),D组优于B组和C组(P<0.05);2、4周B组和C组差异无统计学意义(P>0.05),6周时C组优于B组(P<0.05)。再生神经纤维轴突及髓鞘TGF-β1、IGF抗原染色:A组轻度着色,B、C、D组随观察时间的延长着色逐渐加深。各时间点B、C、D组TGF-β1、IGF抗原表达均较A组高(P<0.05);术后6周,D组与B、C组比较差异有统计学意义(P<0.05),B、C组间比较差异无统计学意义(P>0.05)。HRP逆行示踪实验:随时间延长,被标记的有髓神经纤维逐渐增多,B、C、D组标记阳性的有髓神经纤维数明显高于A组,D组高于其他组,B组和C组差异不明显。结论鹿茸多肽局部应用和鹿茸多肽-PLGA复合膜包绕神经吻合口周围对神经再生均有促进作用,此作用与鹿茸多肽有明显量效关系,鹿茸多肽-PLGA复合膜有预防神经粘连作用。更多还原

【Abstract】 Objective To investigate the velvet antler polypeptide(VAP)on sciatic nerve regeneration in rats through local administration and VAP-PLGA compound membrane.Methods The 3,15 mg/g of VAP-PLGA compound membrane were prepared by compounding VAP and PLGA,respectively.Seventy-two Wistar rats,male or female,aged 3-6 months and weighing(250±50)g,were selected to make the model of sciatic nerve section.Then,all rats were randomized into 4 groups(n=18):group A in which nothing was given after anatomosis,group B in which 1 mL of VAP at the concentration of 10 mg/L was injected into the gastrocnemius muscle medial for every other day,group C in which 3 mg/g of VAP-PLGA compound membrane was given to the nerve anastomotic stoma and group D in which 15 mg/g of VAP-PLGA compound membrane was given to the nerve anastomotic stoma.The sciatic adhesion degree observation,electrophysiological examination,immunohistochemical staining and hemi-quantity calculation and horseradish peroxidase(HRP)retrograde tracing were conducted 2,4 and 6 weeks after operation,respectively.Results All rats survived to the end of the experiment,without foot ulcer or neuroma.Severer nervous adherence was observed in group A,mild adherence in group B,and no adherence in groups C and D 2,4 and 6 weeks after operation,respectively.The recovery rate of the evoked potential of triceps surae in groups B,C and D was better than that in group A(P<0.01),group D was superior to groups B and C(P<0.05)at each time point.No significant difference between group B and group C(P>0.05)2,4 weeks after operation was detected,but group C was superior to group B(P<0.05)6 weeks after operation.For the regenerative fiber axon and the expression of myelin sheath TGF-β 1 and IGF antigen,the staining intensity in groups B,C and D was higher than that in group A at each time point(P<0.05),and there were significant differences between group D and groups B and C 6 weeks after operation(P<0.05),but no difference between groups B and C(P>0.05).The HRP retrograde tracing showed that the myelinated nerve fiber stained by HRP gradually increased as time passed by and myelinated nerve fiber stained by HRP in groups B,C and D was much more than that in group A,and group D was superior to the other groups.No significant difference between group B and group C was detected.Conclusion To apply VAP through either local administration or VAP-PLGA compound membrane around the attached site of nerve anastomosis is capable of promoting nerve regeneration,which has an obvious dose-effect relationship with the dose of VAP.Meanwhile,VAP-PLGA compound membrane can prevent the nerve adhesion.更多还原