短期免疫抑制同种异体肢体移植大鼠周围神经的损伤与再生

Injury and regeneration of rat peripheral nerves with limb transplantation following short-term immunosuppression therapy

背景:肢体移植后肢体生存时间的延长和移植后肢体功能的恢复是关系到肢体同种异体移植能否在临床广泛开展的决定性因素。目的:观察短期免疫抑制治疗对肢体移植后神经再生和功能恢复的影响。方法:将30只SD大鼠随机分为3组。短期组:肢体移植后应用免疫抑制剂14d;长期组:肢体移植后长期应用免疫抑制剂直到取材。对照组单纯肢体移植组术后腹腔内注射生理盐水。术后采用足迹分析、免疫组织化学对组织形态观察评价神经再生和功能恢复的情况。结果与结论:短期组与长期组的功能恢复无明显差别(P>0.05),均明显优于对照组(P<0.05)。组织形态观察显示短期组神经功能恢复优于对照组(P<0.05),短期组与长期组神经纤维再生差异无显著性意义。长期组有3只大鼠因为免疫抑制剂影响导致死亡,对照组与短期组均没有动物模型死亡现象。结果提示,短期应用免疫抑制治疗可迅速减轻周围神经损伤后发生的免疫排斥反应,从而快速改善周围神经损伤后再生的微环境,提高神经的再生速度和质量,取得了与长期应用免疫抑制剂同样的效果而没有致命的不良反应,对于临床应用免疫抑制剂有潜在的意义。

BACKGROUND： It is decisive for limb transplantation carrying out extensively in the clinic whether the immunotolerance and function recovery can be achieved effectively. OBJECTIVE： To investigate the effect of short-term immunosuppression therapy on nerve regeneration and functional recovery following limb transplantation. METHODS： Thirty adult male Sprague Dawley rats were randomly divided into 3 groups. Short-term group： rats received immunosuppression therapy for 14 days after limb transplantation. Long-term group： rats received received immunosuppression therapy for 4 weeks after limb transplantation. Control group： rats received intraperitoneal injection of physiological saline after transplantation. The nerve regeneration and functional recovery were evaluated using footprint analysis, immunohistochemistry and histological observation. RESULTS AND CONCLUSION： There was no obvious difference between the short- and long-term groups in functional recovery （P 0.05）, both of which were superior to the control group （P 0.05）. Results of histological observation suggested that neural functional recovery of the short-term group was better than that of the control group （P 0.05）, but there were no significant differences between the short- and long-term groups in nerve regeneration. Three animals die due to immunosuppressant in the long-term group, no animal lost in the other two groups. The results demonstrated that, short-term immunosuppression therapy can mitigate immunological rejection, improve microenvironment for peripheral nerves regeneration, increase recovery rate and quantity, and reduce adverse reaction, thus, it has a potential for clinical application.