糖皮质激素治疗Duchenne型肌营养不良的疗效及其机制的实验研究

发布时间：2018-03-03 15:23

本文选题：Duchenne型肌营养不良　切入点：糖皮质激素　出处：《重庆医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：探索糖皮质激素(glucocorticoid,GC)治疗Duchenne型肌营养不良(Duchenne muscular dystrophy,DMD)的疗效并明确其可能机制。方法：以mdx小鼠为研究对象，采用随机对照的方法设GC治疗组和安慰剂对照组，通过悬吊试验观察GC治疗后肌力的变化、血清CK值了解肌肉损伤变化、HE染色及电镜观察肌肉组织病理改变；并采用Western blotting检测肌肉组织中utrophin蛋白表达水平变化及其与NF-κB/I-κB、HSP70蛋白表达水平变化的关系。结果：与安慰剂对照组比较，GC治疗后：（1）mdx小鼠的肌力明显提高；血清CK值显著下降(P0.05)；（2）mdx小鼠腓肠肌的病理表现有所减轻；（3）mdx小鼠肌肉组织中HSP70蛋白表达水平及Utrophin蛋白表达水平均有上升(P0.05)，NF-κB蛋白表达水平有下降(P0.05)，而GC治疗后mdx小鼠肌肉组织中I-κB蛋白表达水平与未治疗组比较，，无统计学差异。结论：GC治疗能改善mdx小鼠的肌力；GC可能通过上调HSP70的表达，降低NF-κB的活性，促进utrophin表达，减少肌肉病变。
[Abstract]:Objective: to investigate the effect of glucocorticoid on Duchenne dystrophy and its possible mechanism. Methods: mdx mice were randomly divided into GC treatment group and placebo control group. The changes of muscle strength after GC treatment were observed by suspension test. The changes of serum CK were observed by HE staining and electron microscopy, and the expression of utrophin protein in muscle tissue was detected by Western blotting and its relationship with the expression of NF- 魏 B / I- 魏 BnHSP70 protein. Results: compared with the placebo control group, the muscle strength of the control group was significantly increased after GC treatment. Serum CK decreased significantly in gastrocnemius muscle of P0.05Mdx mice, and the expression of HSP70 protein and Utrophin protein increased in muscle tissue of P0.05Mdx mice. The expression level of NF- 魏 B decreased after GC treatment in the muscle of mdx mice. The expression of I- 魏 B protein in meat tissue was compared with that in untreated group. There was no statistical difference. Conclusion GC can improve the muscle strength of mdx mice by up-regulating the expression of HSP70, decreasing the activity of NF- 魏 B, promoting the expression of utrophin and decreasing the muscle lesion.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R746.2

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