骨骼肌钝挫伤的损伤与修复机制研究进展CSCD

总结骨骼肌钝挫伤的损伤与修复机制,并从肌卫星细胞增殖和分化学说、Ca^(2+)介导的细胞膜修复学说、内质网应激学说以及自噬学说等方面进行阐述。肌再生依赖于周围卫星细胞的分化、增殖来促进骨骼肌再生,从而修复受损肌肉的功能。调控肌卫星细胞成肌分化的相关信号通路主要包括RBP-Jκ/Notch信号、Wnt信号和P13K/Akt/mTOR信号通路。其中Notch信号通路通过调控肌卫星细胞自我更新和分化来维持肌干细胞的稳态。P13K/Akt/mTOR信号通路对肌卫星细胞的成肌分化具有正向调控作用,能够促进骨骼肌再生。然而,当前的研究对Wnt信号通路在成熟骨骼肌再生过程中的作用存在争议,激活Wnt信号通路是否有利于骨骼肌损伤与修复需要更多的研究来进行论证。Ca^(2+)介导细胞膜修复对骨骼肌钝挫伤后肌膜修复、细胞存活至关重要。但是骨骼肌损伤后引起钙泵结构受损或功能下降使Ca^(2+)回收受阻,Ca^(2+)失调通过促进线粒体的活性氧(ROS)的产生和扰乱内质网腔内的蛋白质折叠,有助于异常的蛋白质生成,内质网中异常折叠蛋白生成增多,超过其阈值并发生聚集、滞留,最终诱导内质网过度应激。内质网过度应激可通过PKC或FAM134B途径介导细胞自噬,自噬通过自我降解异常细胞器或错误折叠蛋白,以更新并维持细胞内环境稳态。关于自噬在骨骼肌损伤修复中的作用机制,除了内质网过度应激诱导,有关报道认为钝挫伤诱发的局部组织供氧不足,促使大量的ROS产生或AMPK信号通路的激活,均可诱导线粒体自噬而维持线粒体的稳定,减少能量消耗,从而有利于促进钝挫伤修复。虽然骨骼肌钝挫伤的损伤修复的机制错综复杂,但上述学说之间有交叉之处,因此对于骨骼肌钝挫伤的损伤修复机制研究可以围绕以上学说进一步深入研究,以明确不同学说在骨骼肌损伤修复的不同阶段如何发挥协同作用。

Review on the Injury and Repair Mechanism of Skeletal Muscle Contusions

We reviewed the injury and repair mechanism of skeletal muscle contusions(SMC),it is explained in five aspects,such as the theories of myosatellite cell proliferation and differentiation,Ca²⁺mediated membrane repair,endoplasmic reticulum stress(ERS)and autophagy.Muscle regeneration plays an important role in the repair of SMC,it relies on the differentiation of surrounding satellite cells to restore muscle function.The signal pathways involve in the regulation of myoblast differentiation of myosatellite cells mainly including RBP-Jκ/Notch signal,Wnt signal and P13 K/Akt/mTOR signal pathway.Notch signal pathway regulates the self-renewal and differentiation of myosatellite cells to maintain the homeostasis of muscle stem cells.And P13 K/Akt/mTOR signal pathway has a positive regulation effect on myoblast differentiation of myosatellite cells and can promote skeletal muscle regeneration.However,current research on the role of Wnt signal pathway in the regeneration of mature muscle is controversial,and more studies are needed in the future.Ca²⁺mediated membrane repair is essential for the survival of muscle cells after SMC.Ca²⁺is blocked due to structural damage or functional decline of calcium pump after SMC,leading to calcium depletion in the endoplasmic reticulum(ER).Ca²⁺dysregulation contributes to abnormal protein production by promoting mitochondrial reactive oxygen species(ROS)production and disrupting protein folding in the ER,thus,the abnormal folding protein in the ER is increased.Once the retention and aggregation of which exceeds its threshold value,ERS occurs.Excessive ERS can mediate autophagy through PKC or FAM134 B pathways.Autophagy maintains homeostasis through the self-degradation of abnormal organelles or misfolded proteins.As for the mechanism of autophagy in the repair of SMC,in addition to the induction of excessive ERS,it has been reported that SMC induces insufficient oxygen supply to local tissues,promotes the production of a large number of ROS or activation of AMPK signal pathway,and then induces mitochondrial autophagy,which maintains the stability of mitochondria and saves energy consumption,so as to achieve the purpose of promoting repair after SMC.Although the injury and repair mechanism of SMC is complex,there are some crossovers between the above theories.Therefore,the research on the injury and repair mechanism of SMC can be further explored around the above theories,to clarify how the above different theories play a synergistic role in different stages of injury and repair after SMC.