不同时点A型肉毒毒素干预对脊髓损伤大鼠腓肠肌病理特征影响的研究

摘要

目的:探讨在不同时间点进行A型肉毒毒素(BoNT-A)注射干预对脊髓损伤(SCI)大鼠肌张力(MAS)、运动功能状态(BBB)及腓肠肌(GM)病理特征的影响,进而寻找BoNT-A干预痉挛最佳时间的理论依据.方法:48只SD雄性大鼠被随机分配至Nor-Contrl组、12周-Contrl组、NS干预组和BT干预组.NS/BT干预组按干预时间又分设3个亚组(2周-NS亚组、2周-BT亚组、4周-NS亚组、4周-BT亚组、8周-NS亚组、8周-BT亚组).Nor-Con-trl组和12周-Contrl组大鼠不予注射药物;BT/NS干预组,按上述时间点分别给予BoNT-A/生理盐水注射大鼠右GM.肌张力评估采用MAS评估,运动功能采用BBB评分.GM标本进行肌重测量及蛋白电泳分析(MyHC).结果:与12周-Contrl组相比,BT干预组大鼠GM肌重明显下降(P≤0.05).与12周-Contrl组相比,干预组大鼠MAS及BBB结果差异无显著性意义(P＞0.05).BT干预组中不同亚组大鼠GM的MyHC分型占比较Nor-Contrl组及12周-Contrl组间的差异均有显著性意义(P≤0.05);且随着干预时间点不同,BT干预组大鼠GM的MyHC分型占比亦不同.结论:BoNT-A注射干预导致受注射的GM肌重及肌重/体质量比显著下降,萎缩明显;对受试大鼠MAS及BBB无明显影响;早期注射较后期注射更易引起GM发生MyHC构型改变.%Objective:To explore pathological characteristic of gastrocnemius (GM),BBB motor assessment and MAS of ankle dorsiflexors in spinal cord injury(SCI) model rats which were injected with BoNT-A in different time points.To make sure the proper time for BoNT-A injection.Method:Forty-eight SD male rats (weight 260-280g) were allocated to normal control group,12w-control group,NS-injection group and BT-injection group in this study.NS/BT-therapy groups were divided into three subgroups separately (2w-NS,2w-BT,4w-NS,4w-BT,8w-NS,8w-BT).No injection was applied in normal control group or 12w-control group.Saline / BoNT-A was injected in right GM in NS/BT-therapy group at different time points.MAS was used to assess the ankle dorsiflexors spasticity,BBB was used to assess the movement ability of lower limb.GM at right side of rats would be used for pathological examinations,such as muscle weight and myosin heavy chain electrophoretic analysis.Result:To compared with 12w-contrl group,GM muscle weight decreased significantly in rats of BT injection group (P≤0.05).Comparison with 12w-control group,the two injection groups presented no significant difference of MAS and BBB values(P＞0.05).The differences in MyHC type ratio of GM between BT injection group and Nor-Contrl group and 12w-control group were statistically significant (P≤0.05).Moreover,in each BT injection subgroup,the MyHC type ratio of GM were different with the different time points of injection.Conclusion:BoNT-A injection could result in some changes in GM,such as decreased muscle weight,decreased GM/total weight.No obvious changes were happened in the ankle dorsiflexors spasticity level and the movement ability of lower limb in rats of BT/NS-injection groups.Earlier BoNT-A intervention would induce significant changes on MyHC types characterize than later intervention in GM.