中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (15): 2752-2755.doi: 10.3969/j.issn.1673-8225.2010.15.022　

• 组织构建与生物活性因子 tissue construction and bioactive factors • 上一篇    下一篇

失神经骨骼肌萎缩与氯沙坦通过核因子κB/MuRF1通路的延缓作用

王  乐，梁炳生，李文斌，张  磊，韩利军，吴启平   

  1. 山西医科大学第二医院，山西省太原市  030001
  • 出版日期:2010-04-09 发布日期:2010-04-09
  • 通讯作者: 梁炳生，硕士生导师，博士生导师，山西医科大学附属第二医院骨科，山西省太原市 030001 Liangbs707@yahoo.com.cn
  • 作者简介:王 乐★，男，1983年生，山西省太原市人，汉族，山西医科大学在读硕士，医师，主要从事失神经骨骼肌萎缩研究。 26752042@qq.com

Losartan decreases denervated skeletal muscle atrophy through nuclear factor-kappaB / muscle RING finger protein 1  

Wang Le, Liang Bing-sheng, Li Wen-bin, Zhang Lei, Han Li-jun, Wu Qi-ping   

  1. Second Hospital of Shanxi Medical University， Taiyuan   030001, Shanxi Province, China
  • Online:2010-04-09 Published:2010-04-09
  • Contact: Liang Bing-sheng, Master’s supervisor, Doctoral supervisor, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China Liangbs707@yahoo.com.cn
  • About author:Wang Le★, Studying for master’s degree, Physician, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China 26752042@qq.com

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摘要：

背景：在失神经骨骼肌萎缩中，核因子κB /MuRF1通路是最关键的分子机制之一，抑制该通路可以提高失神经骨骼肌的力量，保持肌肉数量和促进肌肉再生。
目的：探讨核因子κB、MuRF1在失神经骨骼肌中的表达及氯沙坦对核因子κB/MuRF1通路的影响作用，以期寻找延缓失神经骨骼肌萎缩的新途径。
方法：将Wista大鼠随机分为3组：失神经对照组、氯沙坦治疗组建立右下肢失神经腓肠肌动物模型。氯沙坦治疗组大鼠采用氯沙坦以10 mg/(kg•d)空腹灌胃；失神经对照组大鼠以等剂量生理盐水灌胃，以不做处理的大鼠为正常对照。采用RT-PCR和Western Blotting 检测术后2，14，28 d时大鼠腓肠肌核因子κB和MuRF1的mRNA和蛋白表达水平，并结合肌肉失质量比分析其相关性。
结果与结论：大鼠腓肠肌失神经支配后核因子κB和MuRF1的mRNA和蛋白表达在2，14，28 d持续增加(P < 0.05)，而且二因子的表达线性相关有显著性意义(P < 0.05)。失神经支配后14，8 d氯沙坦治疗组腓肠肌湿质量比高于同期失神经对照组(P < 0.05)，氯沙坦治疗组两因子mRNA和蛋白的表达在各个时间点低于失神经对照组(P < 0.05)。核因子κB、MuRF1在失神经肌萎缩中表达增高，而且是同一通路。结果提示氯沙坦可以通过干扰核因子κB、MuRF1mRNA和蛋白质的表达来延缓失神经骨骼肌萎缩。

关键词: 失神经, 肌萎缩, 氯沙坦, 核因子&kappa, B, MuRF1, 肌肉肌腱组织工程

Abstract:

BACKGROUND: Nuclear factor κB (NF-κB)/ muscle RING finger protein1 (MuRF1) pathway is one of the most important molecular mechanisms in skeletal muscle atrophy. Inhibiting of NF-κB / MuRF1 pathway improves denervated skeletal muscle strength, maintains muscle mass, and promotes regeneration.
OBJECTIVE: To explore the expression of NF-κB and MuRF1 in denervated skeletal muscle atrophy in rats and the effect of losartan on NF-κB / MuRF1 pathway.
METHODS: Wistar rats were randomly divided into 3 groups. The denervated and Losartan groups were subjected to establishment of denervated gastrocnemius models followed by normal saline perfusion or losartan 10 mg/kg per day. The control group was not treated. After 2, 14 and 28 days, levels of NF-κB and MuRF1 mRNA and protein in the gastrocnemius were detected respectively by RT-PCR and Western bloting. The ratio of muscle wet weight was also analyzed for comparison.
RESULTS AND CONCLUSION: Expressions of NF-κB and MuRF1 mRNA and protein in denervated skeletal muscle were up-regulated at 2, 14, and 28 days following denervation (P < 0.05). Moreover, NF-κB expression of positively correlated with MuRF1 expression (P < 0.05). At 14 and 28 days after denervation, the losartan group had a greater ratio of muscle wet weight compared with denervated group (P < 0.05). The expression of NF-κB and MuRF1 mRNA and protein in losartan group remarkably reduced compared with denervated group (P < 0.05) at each time point. At the early stage of denervated skeletal muscle atrophy， expression of NF-κB and MuRF1 was up-regulated， suggesting the presence of NF-κB / MuRF1 pathway. Results show that losartan can decrease denervated skeletal muscle atrophy through NF-κB/MuRF1 pathway.

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