• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis but negatively impacts cardiac function
【2h】

Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis but negatively impacts cardiac function

机译：长期向mdx小鼠施用TNF阻断药Remicade（cV1q）可减少骨骼和心肌纤维化但会对心脏功能产生负面影响

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the gene encoding dystrophin (DYS). Tumor necrosis factor (TNF) has been implicated in the pathogenesis of DMD since short-term treatment of mdx mice with TNF blocking drugs proved beneficial; however, it is not clear whether long-term treatment will also improve long-term outcomes of fibrosis and cardiac health. In this investigation, short and long-term dosing studies were carried out using the TNF blocking drug Remicade and a variety of outcome measures were assessed. Here we show no demonstrable benefit to muscle strength or morphology with 10mg/kg or 20 mg/kg Remicade; however, 3mg/kg produced positive strength benefits. Remicade treatment correlated with reductions in myostatin mRNA in the heart, and concomitant reductions in cardiac and skeletal fibrosis. Surprisingly, although Remicade treated mdx hearts were less fibrotic, reductions in LV mass and ejection fraction were also observed, and these changes coincided with reductions in AKT phosphorylation on threonine 308. Thus, TNF blockade benefits mdx skeletal muscle strength and fibrosis, but negatively impacts AKT activation, leading to deleterious changes to dystrophic heart function. These studies uncover a previously unknown relationship between TNF blockade and alteration of muscle growth signaling pathways.
机译：Duchenne肌营养不良症（DMD）是由编码肌营养不良蛋白（DYS）的基因突变引起的变性骨骼肌疾病。肿瘤坏死因子（TNF）参与了DMD的发病机理，因为事实证明，使用TNF阻断剂对mdx小鼠进行短期治疗是有益的。但是，尚不清楚长期治疗是否还会改善纤维化和心脏健康的长期结果。在这项研究中，使用TNF阻断药Remicade进行了短期和长期剂量研究，并评估了多种结果指标。在这里我们没有显示出10mg / kg或20mg / kg的Remicade对肌肉力量或形态有明显的益处；但是，3mg / kg产生了积极的强度益处。杀线虫治疗与心脏肌肉生长抑制素mRNA的减少以及心脏和骨骼纤维化的减少相关。出人意料的是，尽管Remicade处理的mdx心脏的纤维化程度较轻，但也观察到LV质量和射血分数的降低，并且这些变化与苏氨酸308上AKT磷酸化的降低相吻合。因此，TNF阻滞有益于mdx骨骼肌力量和纤维化，但产生了负面影响AKT激活，导致营养不良性心脏功能发生有害变化。这些研究揭示了TNF阻断与肌肉生长信号通路改变之间的先前未知的关系。

著录项

相似文献

  • 外文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号