神经肌肉电刺激对低O2高CO2大鼠下肢骨骼肌miR-1相关通路的影响

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1538 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：探讨神经肌肉电刺激（NMES）对慢性低O2高CO2大鼠腓肠肌的作用，并研究其对miR-1及相关蛋白通路的影响。方法：成年SD大鼠24只随机分成3组：对照组（NC组）、造模组（HH组）和电刺激组（HE组），每组8只。HH组和HE组大鼠置于低O2高CO2舱内造模，每天持续8 h，共4周。HE组在持续造模2周后，用电刺激仪对大鼠进行30 min，2 Hz和100 Hz，1:1交替循环模式的NMES，维持2周；NC组仅做捆绑及贴电极片处理。动物跑台测定大鼠耐力运动能力，免疫组织化学观察腓肠肌肌纤维类型转变，qRT-PCR检测miR-1水平，Western blot检测腓肠肌核内组蛋白脱乙酰基酶4（HDAC4）、肌细胞促进因子2（MEF-2）和过氧化体增殖物激活型受体γ共激活因子1α（PGC-1α）蛋白含量的变化。结果：与NC组比，HH组大鼠腓肠肌慢肌纤维比例明显下降，miR-1含量明显升高，HDAC4、MEF2及PGC-1α蛋白含量明显下降，差异均有统计学意义（P＜0.05）；大鼠耐力运动能力差异无统计学意义（P=0.054）；与HH组比，HE组大鼠腓肠肌慢肌纤维比例明显升高，而miR-1含量下降，对应各蛋白含量均出现不同程度升高，大鼠耐力运动能力也得到了改善，差异均有统计学意义（P＜0.05）。结论：慢性低O2高CO2可致大鼠腓肠肌慢肌纤维向快肌纤维转变，从而导致运动耐力下降，而NMES可部分逆转这种病理变化，改善大鼠耐力运动能力。miR-1-HDAC4-MEF2-PGCα信号通路可能参与其中。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	潘录录
	支英豪
	王小同

关键词 ：低氧高二氧化碳, 慢性阻塞性肺疾病, 神经肌肉电刺激, 组蛋白脱乙酰基酶4, miR-1, 大鼠

Abstract：Objective: To explore the effects of neuromuscular electrical stimulation on gastrocnemius muscle of chronic intermittent hypoxia-hypercapnia (CIHH) rats and try to find out how much the miR-1 related signaling pathway is involved in. Methods: Twenty four male SD rats were randomly divided into three groups: the normal control group (NC), hypoxia-hypercapnia group (HH), hypoxia-hypercapnia+electrical stimulation group (HE). The HH and HE were placed in a chamber with hypoxia-hypercapnia for 8 h/d, 4 weeks in all. After 2 weeks, 30 min, 2 Hz and 100 Hz, 1:1 cyclic alternating pattern of electrical stimulation was applied in the HE, which lasted 2 weeks. The NC was only tied up and placed with electrode plates. The endurance running capacity was assessed by the treadmill. The muscle phenotype was observed by immunohistochemical staining. The expression of miR-1 by qRT-PCR was detected. The expression of HDAC4 (histone deacetylase 4), MEF2 (myocyte enhancer factor 2) and PGC-1α were detected by Western blot. Results: After 4 weeks, the HH group exhibited a decreased MHCI-to-MHCII shift (P<0.05). Nuclear HDAC4, MEF2 and PGC-1α was also significantly decreased (P<0.05). In contrast, miR-1 was significantly increased (P<0.05). Electrical stimulation can partly reversed those changes, and improved endurance running capacity. Conclusion: Our study indicate the miR-1 related signaling pathway may play a role in the response of CIHH-impaired muscle to changes during electrical stimulation.

Key words： chronic intermittent hypoxia-hypercapnia chronic obstructive pulmonary disease neuromu-scular electrical stimulation histone deacetylase 4 miR-1 rats

收稿日期: 2017-10-09

基金资助:浙江省自然科学基金资助项目（Y2080503）。

通讯作者: 王小同，主任医师，教授，Email：wangxt22@163.com。

作者简介: 潘录录（1990-），女，浙江温州人，住院医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I2/86

[1] LEVINE S, BASHIR M H, CLANTON T L, et al. COPD elicits remodeling of the diaphragm and vastus lateralis muscles in humans[J]. J Appl Physiol (1985), 2013, 114(9): 1235-1245. [2] GOSSELINK R, TROOSTERS T, DECRAMER M. Peripheral muscle weakness contributes to exercise limitation in COPD[J]. Am J Respir Crit Care Med, 1996, 153(3): 976-980.
[3] PUENTE-MAESTU L, LAZARO A, HUMANES B. Metabolic derangements in COPD muscle dysfunction[J]. J Appl Physiol (1985), 2013, 114(9): 1282-1290.
[4] GEA J, AGUSTI A, ROCA J. Pathophysiology of muscle dysfunction in COPD[J]. J Appl Physiol (1985), 2013, 114 (9): 1222-1234.
[5] MIN J J, HUO X L, XIANG L Y, et al. Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia expo-sure[J]. Sci Rep, 2014, 4: 5555.
[6] 黄世园, 蒋贤逊, 沈洁, 等. 低频电刺激对低氧高二氧化碳大鼠比目鱼肌肌纤维类型的影响[J]. 温州医科大学学报, 2016, 46(3): 157-162.
[7] 宋菁, 李军, 闵晶晶, 等. ERK和P38在慢性低氧高二氧化碳小鼠骨骼肌凋亡中的作用[J]. 中国细胞生物学学报, 2013, 35(4): 432-436.
[8] CHEN J F, MANDEL E M, THOMSON J M, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation[J]. Nat Genet, 2006, 38(2): 228-233.
[9] KOCH L G, BRITTON S L. Artificial selection for intrinsic aerobic endurance running capacity in rats[J]. Physiol Genomics, 2001, 5(1): 45-52.
[10] GULLER I, RUSSELL A P. MicroRNAs in skeletal muscle: their role and regulation in development, disease and function[J]. J Physiol,2010, 588(Pt 21): 4075-4087.
[11] LEWIS A, RIDDOCH-CONTRERAS J, NATANEK S A, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD[J]. Thorax, 2012, 67(1): 26-34.
[12] COHEN T J, BARRIENTOS T, HARTMAN Z C, et al. The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity[J]. FASEB J, 2009, 23(1): 99-106.
[13] ROBERTS-WILSON T K, REDDY R N, BAILEY J L, et al. Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes[J]. Biochim Biophys Acta, 2010, 1803(8): 960-967.
[14] LIN J, WU H, TARR P T, et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres[J]. Nature, 2002, 418(6899): 797-801.
[15] ZHAO X, ITO A, KANE C D, et al. The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking[J]. J Biol Chem, 2001, 276(37): 35042-35048.
[16] SUN Y, GE Y, DRNEVICH J, et al. Mammalian target of rapamycin regulates miRNA-1 and follistatin in skeletal myo-genesis[J]. J Cell Biol, 2010, 189(7): 1157-1169.
[17] CASABURI R, PORSZASZ J, BURNS M R, et al. Physiologic benefits of exercise training in rehabilitation of patients with severe chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 1997, 155(5): 1541-1551.
[18] VIVODTZEV I, DEBIGARE R, GAGNON P, et al. Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: A randomized clinical trial[J]. Chest, 2012, 141(3): 716-725.