Yin Xi, Tang Ying, Li Jian, Dzuricky Anna T, Pu Chuanqiang, Fu Freddie, Wang Bing
Department of Orthopaedic Surgery, University of Pittsburgh, Suite 216, Bridgeside Point II, 450 Technology Drive, Pittsburgh, Pennsylvania, 15219, USA.
Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, China.
Muscle Nerve. 2017 Oct;56(4):759-767. doi: 10.1002/mus.25517. Epub 2017 May 15.
Duchenne muscular dystrophy (DMD) is a genetic muscle disease characterized by dystrophin deficiency. Beyond gene replacement, the question of whether ablation of the p65 gene of nuclear factor-kappa B (NF-κB) in DMD can improve muscle physiology function is unknown. In this study, we investigated muscle physiological improvement in mdx mice (DMD model) with a genetic reduction of NF-κB.
Muscle physiological function and histology were studied in 2-month-old mdx/p65 , wild-type, mdx, and human minidystrophin gene transgenic mdx (TghΔDys/mdx) mice.
Improved muscle physiological function was found in mdx/p65 mice when compared with mdx mice; however, it was similar to TghΔDys/mdx mice. The results indicate that genetic reduction of p65 levels diminished chronic inflammation in dystrophic muscle, thus leading to amelioration of muscle pathology and improved muscle physiological function.
The results show that inhibition of NF-κB may be a promising therapy when combined with gene therapy for DMD. Muscle Nerve 56: 759-767, 2017.
杜氏肌营养不良症（DMD）是一种以肌营养不良蛋白缺乏为特征的遗传性肌肉疾病。除了基因替代疗法外，DMD中核因子-κB（NF-κB）的p65基因缺失是否能改善肌肉生理功能尚不清楚。在本研究中，我们研究了NF-κB基因表达降低的mdx小鼠（DMD模型）的肌肉生理改善情况。
对2月龄的mdx/p65小鼠、野生型小鼠、mdx小鼠和人类微小肌营养不良蛋白基因转基因mdx（TghΔDys/mdx）小鼠的肌肉生理功能和组织学进行了研究。
与mdx小鼠相比，mdx/p65小鼠的肌肉生理功能有所改善；然而，其与TghΔDys/mdx小鼠相似。结果表明，p65水平的基因表达降低减少了营养不良性肌肉中的慢性炎症，从而改善了肌肉病理并提高了肌肉生理功能。
结果表明，抑制NF-κB与DMD基因治疗联合使用时可能是一种有前景的治疗方法。《肌肉与神经》56: 759 - 767, 2017年。
