外源性促红细胞生成素对失神经骨骼肌萎缩的影响

EFFECT OF EXOGENOUS ERYTHROPOIETIN ON DENERVATED MUSCLE ATROPHY

目的探讨外源性促红细胞生成素(erythropoietin,EPO)对失神经骨骼肌萎缩的影响。方法取雄性SD大鼠24只,体重200～220g,于右侧梨状肌下缘切断坐骨神经,制备小腿三头肌失神经支配模型。模型制备后随机分为两组(n=12),EPO组:术后每天右小腿腓肠肌注射rhEPO(2500U/kg);对照组:注射等体积生理盐水。术后观察动物一般情况,于第2、4周检测肌湿重、肌肉蛋白含量,行HE及TUNEL染色,测量肌细胞直径、横切面积及细胞凋亡率,并测定肌肉Na+-K+-ATP酶和Ca2+-ATP酶活性。结果术后两组动物右后肢均拖膝行走,切口无感染,动物均存活至实验完成,4周时对照组5只及EPO组2只大鼠发生足跟溃疡。术后2、4周EPO组肌湿重分别为(885.59±112.35)、(697.62±94.74)g,均明显重于对照组(760.63±109.05)、(458.71±58.76)g(P<0.01);肌肉蛋白含量分别为(77.37±5.24)、(66.37±4.87)mg/mL,明显高于对照组(65.39±4.97)、(54.62±6.32)mg/mL(P<0.01)。术后2、4周EPO组肌纤维形态基本正常;对照组肌纤维萎缩变细,部分断裂,肌束间结缔组织增生较明显;EPO组肌细胞直径和横切面积明显大于对照组(P<0.01)。术后2、4周,EPO组骨骼肌细胞凋亡数明显少于对照组,EPO组腓肠肌细胞凋亡率分别为11.80%±1.74%、28.47%±1.81%,明显低于对照组21.48%±2.21%、55.89%±2.88%(P<0.01)。术后2、4周EPO组Na+-K+-ATP酶和Ca2+-ATP酶活性均高于对照组(P<0.01)。结论EPO具有明显延缓大鼠失神经骨骼肌萎缩的作用。

Objective To investigate theffeffect of exogenous erythropoietin （EPO） on the denervated muscle atrophy. Methods Twenty-four SD male rats,weighting 200-220 g were made the models of denervated gastrocnemius muscle after sciatic nerves were transected under the piriform muscle at the right lower leg,and were randomly divided into two groups （n=12）. rhEPO （2 500 U/kg） was injected daily into the denervated gastrocnemius muscle in EPO group,and normal saline was injected into the denervated gastrocnemius muscle in control group. To observe the general state of health of theffexperimental animal,the muscle wet weight,the muscle cell diameter,the cross section area,the protein amount,the percentage of the apoptotic muscle cells,and the Na＋-K＋-ATPase and Ca2＋-ATPase activities were measured 2 and 4 weeks after operation. Results All experimental animals were survived during experiment without cut infection,and all animals could walk with pulling the right knee. At 4 weeks after operation,7 cases showed ulcer in the right heel,inculding 5 in the control group and 2 in the EPO group. At 2 and 4 weeks after operation,the muscle wet weight in EPO group was （885.59 ± 112.35） and （697.62 ± 94.74） g,respectively; in control group,it was （760.63 ± 109.05） and （458.71 ± 58.76） g,respectively; indicating signi cant di erences between two groups （P 〈 0.01）. The protein amount in EPO group was （77.37 ± 5.24） and （66.37 ± 4.87） mg/mL,respectivly;in control group,it was （65.39 ± 4.97） and （54.62 ± 6.32） mg/mL;indicating signi cant di erences between two groups （P 〈 0.01）. At 2 and 4 weeks after operation,the myo brillar shapes were nearly normal in EPO group while there were muscle ber atrophy,some collapse and obviously hyperblastosis between muscle bundle. There were signi cant di erences in the muscle cell diameter and the cross section between two groups （P 〈 0.01）. However,the percentage of the apoptotic muscle cells was 11.80% ± 1.74% and 28.47% ± 1.81% in control group,respectively,which was signi cantly smaller than that in EPO group （21.48% ± 2.21% and 55.89% ± 2.88%,P 〈 0.01）. At 2 and 4 weeks after operation,Na＋-K＋-ATPase and Ca2＋-ATPase activities in EPO group were higher than those in control group （P 〈 0.01）. Conclusion EPO can delay the denervated muscle atrophy.