Smad3通过抑制免疫炎症反应延缓去神经导致的肌肉萎缩  

Smad3 alleviates denervation-induced muscular atrophy by suppressing the immune inflammatory response

作　　者：符之月 季玉陈 周世玲 寇冬权 李明 FU Zhiyue;JI Yuchen;ZHOU Shiling;KOU Dongquan;LI ming(Department of Respiratory Medicine,Qionghai People’s Hospital,Qionghai 571400,China;Department of Neurosurgery,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Neurology,Qionghai People’s Hospital,Qionghai 571400,China;Department of Rehabilitation Medicine,Chongqing Public Health Medical Treatment Center,Chongqing 400000,China;Department of Orthopedics,First Affiliated Hospital of Hainan Medical University,Haikou 570102,China)

机构地区：[1]琼海市人民医院呼吸内科,571400 [2]琼海市人民医院神经内科,571400 [3]郑州大学第一附属医院神经外科,450052 [4]重庆市公共卫生医疗救治中心康复医学科,400000 [5]海南医学院附属第一医院骨科,海口570102

出　　处：《免疫学杂志》2021年第9期766-772,共7页Immunological Journal

摘　　要：目的初步探讨Smad3通过抑制免疫炎症反应保护去神经导致的肌肉萎缩及其相关机制。方法构建小鼠后肢神经切除导致的肌肉萎缩模型,应用RT-PCR检测小鼠肌肉组织中肌肉萎缩标志基因Atrogin-1和MuRF-1的表达,Western blot检测小鼠肌肉组织中Smad3蛋白表达变化。小鼠后肢注射Smad3激动剂后进行神经切除手术或者使用Smad3抑制剂SIS3 HCl进行上述相同的功能逆转实验,1周后,应用RT-PCR检测小鼠肌肉组织中IL-1β、TNF-α、Atrogin-1和MuRF-1的表达。基于小鼠后肢神经切除导致的肌肉萎缩模型和包装纯化过表达Smad3 AAV8腺相关病毒进行治疗效果探索,应用Western blot检测小鼠肌肉组织中Smad3蛋白表达变化,RT-PCR检测小鼠肌肉组织中Atrogin-1和MuRF-1的表达。结果Western blot实验显示,小鼠去神经导致的肌肉萎缩中Smad3表达降低。RT-PCR实验显示,过表达Smad3能够明显抑制小鼠去神经导致的肌肉萎缩中IL-1β、TNF-α、Atrogin-1和Mu RF-1的表达,抑制Smad3能够明显促进小鼠去神经导致的肌肉萎缩中IL-1β、TNF-α、Atrogin-1和MuRF-1的表达。此外,RT-PCR实验显示,过表达Smad3 AAV8腺相关病毒减弱去神经导致的肌肉萎缩。结论Smad3能够通过抑制炎症因子IL-1β、TNF-α的表达延缓去神经导致的肌肉萎缩。This study was designed to investigate the effects of Smad3 on denervation-induced muscular atrophy by suppressing the immune inflammatory response and to explore the related mechanism.The model of denervation-induced muscle atrophy was established by neuronectomy of the hind limb in mice,and the expression of muscle dystrophy marker genes Atrogin-1 and MuRF-1 in the muscle tissues were detected by RT-PCR.The expression of Smad3 in the muscle tissues were detected by Western blotting.Mice were pretreated with Smad3 agonist(alantolactone)/inhibitor(SIS3 HCl),and then used for establishment of denervation-induced muscular atrophy.After one week,RT-PCR was used to detect the expression of IL-1β,TNF-α,Atrogin-1 and MuRF-1 in the muscle tissues.Furthermore,the therapeutic effect was explored by using the mouse model of muscle atrophy induced by neuronectomy of the hind limb and AAV8 adeno-associated virus overexpressing Smad3.The expression of Smad3 in the muscle tissues were detected by Western blotting,and the expression of Atrogin-1 and MuRF-1 in the muscle tissues were detected by RT-PCR.Westernblot showed that the expression of Smad3 in the muscletissues was decreased in denervation-inducedmuscular atrophy mice.RT-PCR showed thatoverexpression of Smad3 could significantly inhibit the expression of IL-1β,TNF-α,Atrogin-1 and MuRF-1 in denervation-induced muscle atrophy mice,while inhibitionof Smad3 could significantly promote the expression of IL-1β,TNF-α,Atrogin-1 and Mu RF-1 in denervation-induced muscle atrophy mice.In addition,RT-PCR showed that overexpression of Smad3 AAV8 adeno-associatedvirus attenuated denervation-induced muscular atrophy.Taken together,Smad3 inhibits denervation-inducedmuscular atrophy by inhibiting the expression of inflammatory cytokines IL-1βand TNF-α.

关 键 词：SMAD3 炎症因子 去神经导致的肌肉萎缩 

分 类 号：R392.7[医药卫生—免疫学]