地夫可特改善杜氏肌营养不良症小鼠运动能力及减轻肌肉炎症损伤  

Deflazacort improves locomotion and reduces muscle inflammatory damage in mice with duchenne muscu⁃lar dystrophy

作　　者：杨晓 张欢 张朝晖 杨细飞 YANG Xiao;ZHANG Huan;ZHANG Zhaohui;YANG Xifei(School of Public Health,Hengyang Medical School,University of South China,Hengyang 421001,China;不详)

机构地区：[1]南华大学衡阳医学院公共卫生学院,湖南衡阳421001 [2]深圳市疾病预防控制中心深圳市现代毒理学重点实验室,深圳市卫生毒理学医学重点学科,广东深圳518055

出　　处：《实用医学杂志》2023年第13期1614-1619,1626,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82171583);深圳市科技创新委员会重点基础研究计划项目(编号:JCYJ20200109150717745XY);深圳市医学重点学科建设经费资助(编号:SZXK069),深圳市医疗卫生三名工程项目(编号:SZSM201611090)。

摘　　要：目的了解杜氏肌营养不良症(DMD)小鼠的运动能力和骨骼肌病理改变,探索地夫可特(Deflazacort)对DMD的治疗效果。方法选取10周龄转基因DMD小鼠,根据体重随机分为正常组、模型组、地夫可特组。每组7只,实验周期8周,小鼠每周称重1次。在小鼠10周龄、14周龄和18周龄时,通过悬挂测试、爬杆测试、抓握力测试评估小鼠运动能力。18周龄时采取步态测试分析小鼠四肢步幅距离和步行速度变化。小鼠安乐死后,通过检测血清肌酸激酶、乳酸脱氢酶、肌肉病理组织学和形态学分析评估肌肉病变情况。结果与模型组小鼠相比,地夫可特组小鼠体质量无显著变化、悬挂时间延长(P<0.05)、爬杆耗时减少(P<0.01)、前肢抓力增大(P<0.05)、步幅距离和步行速度增加(P<0.01)、血清肌酸激酶值降低、骨骼肌炎性细胞浸润面积(P<0.01)和纤维化面积减少。结论地夫可特治疗具有改善DMD小鼠运动功能减退,步态缓滞失衡和骨骼肌炎症损伤的作用。Objective To investigate the motor ability and skeletal muscle pathology in mice with Duch⁃enne muscular dystrophy(DMD)and to explore the therapeutic effects of Deflazacort on DMD.Methods Ten⁃weeks⁃old transgenic DMD mice were selected and randomly divided into normal control group,model group and Deflazacort⁃treated group according to their body weights,seven in each group.The mice in all groups were weighed once a week for an experimental period of 8 weeks.At 10,14 and 18 weeks of age,the mice were assessed for locomotor activity by hanging test,pole climbing test and grip strength test,and at 18 weeks of age,the mice were observed for changes in limb stride distance,followed by testing their walking speeds by gait test.After eutha⁃nasia,muscle lesions were assessed by measuring serum creatine kinase,lactate dehydrogenase,muscle pathology histology and morphological analysis.Results Compared to the DMD mice,there were no significant changes in body weight in Deflazacort⁃treated mice,but the suspension time was prolonged(P<0.05),the pole climbing elapsed time reduced(P<0.01),the forelimb grip increased(P<0.05),and the stride distance and walking speed both increased(P<0.01).Meanwhile,the serum creatine kinase values were lowered,and the areas of skeletal muscle inflammatory cell infiltration(P<0.01)and fibrosis were reduced.Conclusion Deflazacort is effective in treating hypokinesia,gait bradykinesia and skeletal muscle inflammatory damage in mice with DMD.

关 键 词：地夫可特 杜氏肌营养不良症 运动能力 骨骼肌损伤 炎症 

分 类 号：R685[医药卫生—骨科学]