原矾酸钠改善mdx鼠骨骼肌运动功能的研究及其机制探索  

Exploration of sodium orthovanadate in improving the motor function of skeletal muscles and its mechanism in mdx mice

作　　者：郑卉[1] 李秋玲[2] 杨娟[3] 操基清[4] 梁颖茵[4] 李亚勤[4] 张惠丽[4] 朱瑜玲 张成[4] 

机构地区：[1]南方医科大学南方医院神经内科,广州510515 [2]广东省人民医院儿科,广州510080 [3]南方医科大学珠江医院神经内科,广州510280 [4]中山大学附属第一医院神经内科,广州510080

出　　处：《中华神经医学杂志》2013年第12期1259-1265,共7页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金博士启动项目f$2011040003104）;国家自然科学基金青年基金项目（81100938-H0911）

摘　　要：目的探索原矾酸钠（soy）能否增强骨骼肌的运动功能及其可能的作用机制。方法以73只mdx鼠为研究对象，按照SOV注射剂量的不同将其分为0mg／kg（阴性对照组）及3、9、12、15、18和21mg／kgSOV治疗组，另选10只C57BL／10小鼠作为正常对照组。连续尾静脉注射S0v2次后，用生物机能实验系统BL-420E检测mdx鼠骨骼肌运动功能的改变，并分别用CK试剂盒、HE染色和免疫组化检测各组血清肌酸激酶（CK）值、肌肉病理特点和dystrophin表达。结果与阴性对照组比较，SOV12和SOV15两组胫前肌的肌肉收缩力升高了20％～30％，SOV9、SOV12和SOV15组的运动单位动作电位（MUAP）波宽减小了约50％．治疗组MUAP波幅最高增大1．8mV，SOV12和SOV15组的MUAP相数减少至2相，差异有统计学意义（P〈0．05）。与阴性对照组比较，SOV9、SOV12和sOV15组血清CK值明显降低（最高可达65％），差异有统计学意义（P〈0．05）。与阴性对照组比较，SOV9、SOV12和SOV15组的肌肉病理改善最为明显，核中移肌纤维的数量降至52％．58％，差异有统计学意义（p／0．05）；而这3组炎性细胞的浸润也有一定程度的减轻。结论SOV能通过抑制Na＋-K＋ATP酶的活性改善肌肉的运动功能，降低血清CK值，缓解肌纤维的变性坏死和炎性细胞浸润，提示其可能成为潜在治疗肌肉疾病的药物。Objective To explore whether sodium orthovanadate （SOV） can improve the motor function of skeletal muscle and its mechanism. Methods Seventy-three mdx mice were chosen in our study and divided into negative control group, and 3, 9, 12, 15, 18 and 21 mg/kg SOV treatment groups according to the injection dosages of SOV; another 10 C57BL/10 mice were chosen as healthy control group. After twice injection, the changes of their motor functions were detected by Biological and Functional Experimental System BL-420E. In addition, creatine kinase （CK） reagent kit, HE staining and immunohistochemistry were used to observe the serum CK level, pathology features of skeletal muscles and dystrophin expression. Results As compared with that in the mdx mice, the contractility oftibialis anterior （TA） muscles in the 12 and 15 mg/kg SOV treatment groups obviously improved 20%-30%, the duration of motor unit action potential （MUAP） in 9, 12 and 15 mg/kg SOV treatment groups was significantly shortened about 50%, the amplitude in all the treatment groups was enlarged to 1.8 mV and the phases in the 12 and 15 mg/kg SOV treatment groups decreased to 2 phases, with significant differences （P〈0.05）. The serum CK level in the 9, 12 and 15 mg/kg SOV treatment groups was significantly decreased, some reaching to 65%, as compared with that in the mdx mice. The central nucleation in the 9, 12 and 15 mg/kg SOV treatment groups was significantly alleviated as compared with that in the mdx mice （P〈0.05）; and the inflammation infiltration of involved muscles in mdx mice was severer. However, the unconformity of muscular fibers did not ameliorate and the dystrophin positive fibers did not increase in the SOV treatment groups as compared with those in mdx mice （P〉0.05）. Conclusion SOV cannot improve the the motor function of mdx mice through inhibiting Na＋-K＋-ATPase activity, decrease the CK level and relieve the muscle fiber necrosis and inflammatory cell infiltration, therefore, SOV can probably be a potenti

关 键 词：DUCHENNE型肌营养不良症 原矾酸钠 运动单位动作电位 肌肉收缩力 NnK+-ATP酶抑制剂 

分 类 号：R746[医药卫生—神经病学与精神病学]