骨骼肌2016

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1 思考题 - 课堂提问周测及应用课前测试 ( 主要关节见后面 PPT 所示 ): 画图 : 选择一个重要关节, 画出主要附着肌肉及解释功能肌肉主要组织结构有哪些 ( 组织细胞 ) Which types of stem cells could be used for skeletal muscle disorders 题目没有标准的答案, 但有要点, 答中要点即可

2 人体结构与功能学 Human Anatomy and Physiology 运动系统 / 肌肉骨骼系统 Locomotor system/musculoskeletal system

3 骨学 Osteology 关节学 Arthrology 肌学 Skeletal muscle

4 人体结构与功能学 Human Anatomy and Physiology Skeletal Muscle Tissue 骨骼肌陈晓浙江大学医学院李达三叶耀珍干细胞与再生医学研究中心临床医学运动医学博士

5 人类所有改造世界改造自己的意识活动都需要通过骨骼肌运动实现

6 2015

9 骨骼肌常见疾病 : 难以治疗肌肉创伤 : 肌肉损伤肌腱损伤 ( 刘翔, 肩周炎 ), 一半以上的肌肉骨骼系统创伤肌肉衰老 : 老年性变化的主要特征之一, 易摔倒导致骨折及其他损伤

10 骨骼肌常见疾病 : 难以治疗神经原性肌萎缩 ( 霍金, 肌肉萎缩性侧索硬化症 ) 常见肌病 : 重症肌无力进行性肌营养不良周期性瘫痪肌肉萎缩

11 冰桶挑战

12 课程设置 -- 骨骼肌理论课程内容,2.5 学时课程目标 : 能分析大关节运动时肌肉力学模式从肌肉肌腱组织结构分析损伤时修复的策略总论 : 人体的重要骨骼肌分布分类和生物力学模型一肌肉的构造与各部分的功能 : 肌腹肌腱神经血管, 筋膜二肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质 ( 胶原, 多糖, 糖蛋白 ) 三肌肉的收缩机制和功能四肌肉营养生长维持和愈合过程

13 课程设置 -- 骨骼肌课程内容总论 : 人体的重要骨骼肌分布分类和生物力学模型一肌肉的构造与各部分的功能 : 肌腹肌腱神经血管, 筋膜二肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质( 胶原, 多糖, 糖蛋白 ) 三肌肉的收缩机制和功能四肌肉营养生长维持和愈合过程

14 思考题 - 课堂提问周测及应用课前测试 ( 主要关节见后面 PPT 所示 ): 画图 : 选择一个重要关节, 画出主要附着肌肉及解释功能肌肉主要组织结构有哪些 ( 组织细胞 ) Which types of stem cells could be used for skeletal muscle disorders 课堂提问 : 主要肌群名字及功能肌肉肌膜肌腱, 血管神经构成 ( 可解释 ) 分别由成熟细胞与干细胞构成 : 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞自体异体肌卫星细胞, 肌肉干细胞,IPS, MSC,ESC 等等

15 思考题 - 课堂提问周测及应用周测 : 学习完后可应用知识分析日常生活临床损伤 (1,2, 3) 及研究 (4)( 简答题 100 字左右描述, 也可自由发挥, 有不理解处请提问 ) 若想拥有施瓦辛格式的胸肌, 请从相关肌肉及关节的类型功能做出肌肉运动的力学模型及实际动作 ( 从人体主要肌群的功能解释肌肉针对性训练的动作, 选一 : 股四头肌, 胸大肌, 肱二头肌等 ) 从肌肉 - 骨形成的力学杠杆特性简述各种关节的运动特征 ( 选一 ): 力学强度运动速度, 灵活性及从关节所受力学分析其易损伤程度 ( 肩, 肘膝, 踝关节 ) 根据弯腰时背部肌肉收缩对椎间盘的压力模式, 估计竖脊肌收缩时椎间盘所受的压力 ( 特别是搬重物, 坐车时颠簸等等常见不正确姿势 ), 如何避免生活中椎间盘急性及慢性损伤 ( 上两题为包括关节学内容, 关节课程有讨论, 主要为服务于是生活, 可只回答肌肉 - 关节力学杠杆模式 ) 简述肌肉肌腱组织干细胞种类, 并简要分析及在损伤修复过程中应用

16 Pandect muscle system 1/3 OF HUMAN BODY Skeletal 骨骼肌 only voluntary muscle tissue ( 自主运动 ) Striated 横纹肌 Heart 心肌 Involuntary Striated Smooth 平滑肌 Involuntary Non-Striated

17 Pandect skeletal muscle system properties Contractible Extensible Excitable Function Action of body: Powerful contraction (100W/Kg) Joint stabilization Heat

18 Do you know the magic power of your muscles? Cherish your health and bodies!! 衰老导致肌力协调力下降是摔倒主因 :do exercise to delay aging!!! How and why you can anti-aging??? 1.Jonas Rantanen 深蹲 575 公斤 2.Donnie Thompson 深蹲 573 公斤 3 VladislavAlhazov 深蹲 567 公斤 4Mike Miller 深蹲 553 公斤正常成年人肌肉的力量 : How about you,..100kg? 40N/cm2,10-20t/ person why don t you know you are so strong?? 人类不借外力和杠杆作用所能移动的最大重量 : 腿举 Jeff 1870 Lewis 公斤 ( 德国大力士台式腿举 Hermann 吨? Gorner)

19 Pandect classify of skeletal muscle type Size: vastus(huge); maximus(large); longus(long); minimus(small); brevis (short). Shape:deltoid (triangular 三角肌 ); rhomboid (like a rhombus with equal and parallel sides); latissimus(wide); teres(round); trapezius ( 斜方肌 like a trapezoid, a four-sided figure with two sides parallel). Direction of fibers:rectus (straight); transverse (across); oblique (diagonally); orbicularis (circular). Location:pectoralis(chest); gluteus (buttock or rump 臀肌 ); brachii(arm); supra- (above); infra-(below); sub-(under or beneath); lateralis(lateral). Number of origins:biceps (two heads); triceps (three heads); quadriceps (four heads). Origin and insertion:sternocleidomastoideus(origin on the sternum and clavicle, insertion on the mastoid process 胸锁乳突肌 ); brachioradialis(origin on the brachium or arm, insertion on the radius 肱桡肌 ). Action:abductor (to abduct a structure 展肌 ); adductor (to adduct a structure); flexor (to flex a structure); extensor (to extend a structure); levator(to lift or elevate a structure); masseter (a chewer).

In somemuscles the fibers are parallel to the long axis of the

20 Pandect morphological skeletal muscle type 短肌长肌轮匝肌二腹肌阔肌羽状肌 Some skeletal muscles are broad in shape and some narrow. In somemuscles the fibers are parallel to the long axis of the muscle; in some they converge to a narrow attachment; and in some they are oblique: 请举例

21 Pandect skeletal muscle mechanical model Muscle Muscle-tendon junction Tendon Tendon bone junction Typical skeletal muscle structure Force by muscle contraction

22 从重要关节分析重要肌肉的分布及功能 shoulder joint 肩关节 : pectoralismajor 胸大肌, 三角肌, 斜方肌, 背阔肌, 肩袖相关肌肉 ( 视频资料均来自互联网,30m) Elbow 肘关节 : 肱二头肌 biceps brachii, 肱三头肌, 前臂群脊柱 : 竖脊肌 erector spinae 髋膝踝关节 : 臀大肌内收肌群, 股四头肌 quadriceps femoris 小腿三头肌, ( 伸肌群 )

23 Pandect skeletal muscle mechanical model muscle lever system First class lever: elbow( 肘关节 ) 动力点阻力点分别在支点的两边

24 Pandect skeletal muscle mechanical model Second class lever: ankle joint( 踝关节 ) 省力杠杆 Third class lever: elbow ( 肘关节 ) 费力杠杆

25 课程设置 -- 骨骼肌课程内容总论 : 人体的重要骨骼肌分布分类和生物力学模型一肌肉的构造与各部分的功能 : 肌腹肌腱神经血管, 筋膜二肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质( 胶原, 多糖, 糖蛋白 ) 三肌肉的收缩机制和功能四肌肉营养生长维持和愈合过程

26 肌肉的结构与功能 From single molecular to muscle tissue

27 Structure of muscle : from whole muscles to myofilaments Macro- structure: Muscle tissue, nerve, vascular etc. Micro- structure Muscle cells, blood, ECM Ultra-structure: myosin

28 Structure of muscle tissue A whole skeletal muscle is considered an organ of the muscular system: 肌肉结构相关视频 ( 视频资料均来自互联网 ) skeletal muscle tissue: 肌腹 nerve tissue connective tissue blood or vascular tissue. 肌束膜肌纤维肌腱肌外膜肌内膜筋膜

29 Function of muscle tissue Contract to create force: 肌纤维收缩视频 Move body Stable body

Structure and Function of Nerve tissue Nerve tissue:

proprioceptive information http://baike.baidu.

30 Structure and Function of Nerve tissue Nerve tissue: Neuromuscular spindle, neuromuscular junction Neuromuscular spindle 肌梭 1mmX mm Essential for controlling muscle contraction proprioceptive information 8ccbf6c81810a4c87.html#albumindex=0&picindex=0

31 Structure and Function of Nerve tissue Histology of Neuromuscular spindle

32 Structure and Function of Nerve tissue: neuromuscular junction neuromuscular junction 神经肌肉接头, 终板神经肌肉信号传递视频 Terminals of motor neurons Release neurotransmitter to control muscle contraction Nutrition

33 Function of nerve tissue on muscle determination: Innervate muscles 营养性作用切断运动神经后, 肌肉因失去神经的营养性作用而出现萎缩将支配慢肌和支配快肌的神经分别切断, 然后将支配快肌的中枢端与支配慢肌的神经的外周缝合, 待神经再生后, 慢肌就可转变成快肌 Question: 如何延缓肌肉衰老? 机体自己并不知道如何保持肌肉的修复功能 80 岁的男性平均损失 40% 的肌肉重量, 上了年纪的人容易摔倒或骨折并因此住院治疗在医院他们又会失去更多的肌肉力量, 而且不会再恢复 50m

Structure and Function of Nerve tissue Golgi tendon organs: 500X100um Losser collagen fibers Larger fibroblasts Near MTJ( 肌肉 - 肌腱连接 ) Activated by stretch of the tendon Providing proprioceptive

34 Structure and Function of Nerve tissue Golgi tendon organs: 500X100um Losser collagen fibers Larger fibroblasts Near MTJ( 肌肉 - 肌腱连接 ) Activated by stretch of the tendon Providing proprioceptive information( 本体感觉, 位置 ) Very sensitive (much higher than muscles) No one knows its function on tendon regeneration and development Question : what is your opinion on Golgi tendon organs regeneration?

Blood supply of muscle Abundant Generally, an artery and at least one vein accompany each nerve that penetrates the epimysium of a skeletal muscle.

35 Blood supply of muscle Abundant Generally, an artery and at least one vein accompany each nerve that penetrates the epimysium of a skeletal muscle. Branches of the nerve and blood vessels follow the connective tissue components of the muscle of a nerve cell and with one or more minute blood vessels called capillaries

36 Blood supply of muscle Classification of blood supply

Connective tissue: Tendon Tendon: Dense fibrous

Transmit the forces when movement Heterogeneous

vascular cells smooth muscle cells capillary

37 Connective tissue: Tendon Tendon: Dense fibrous connective tissue Connect muscle to bone Transmit the forces when movement Heterogeneous fibril diameter and crimp pattern Structure Cells collagen molecules tendon cells (tenocytes) chondrocytes synovial cells vascular cells smooth muscle cells capillary endothelial cells 2016 年 10 月 10 日星期一 1 时 27 分 57 秒 Structure of collagen 37

38 Tendon biology Biomechanics 17 to 117 MPa (Ultimate tensile stress) 100 to 1400MPa (Linear modulus) Energy-storing In vivo peak forces (10% - 30% of failure forces) 2016 年 10 月 10 日星期一 1 时 27 分 57 秒 stress strain curve

39 课程设置 -- 骨骼肌课程内容总论 : 人体的重要骨骼肌分布分类和生物力学模型一肌肉的构造与各部分的功能 : 肌腹肌腱神经血管, 筋膜二肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质( 胶原, 多糖, 糖蛋白 ) 三肌肉的收缩机制和功能四肌肉肌腱营养生长维持和愈合过程

40 肌肉的组织成分与功能肌细胞

41 Structure of muscle : from whole muscles to myofilaments Macro- structure: Muscle tissue, nerve, vascular etc. Micro- structure Muscle cells, blood, ECM Ultra-structure: myosin

be made up of hundreds, or even thousands, of

42 Muscle cells, core of skeletal muscles contraction mechanism Each skeletal muscle fiber is a single cylindrical muscle cell. Very large cell An individual skeletal muscle may be made up of hundreds, or even thousands, of muscle fibers bundled together and wrapped in a connective tissue covering.

43 Muscle cells, contraction mechanism TEM TEM contraction 细肌丝向粗肌丝滑行肌动蛋白收缩相关视频

44 Structure of muscle fibers

46 Structure and Function of muscle tissue 粗肌丝细肌丝 myosin heavy chain divided into type I, type IIa, type IIx, and type Iib Question: why 博尔特 run so fast?

47 肌肉收缩机制肌肉收缩机制 ( 视频解说 )

48 Summary : muscle tissue, from single molecular to tissue

49 Other cells in skeletal muscle 30m

50 Other cells in muscle and tendon and their function 肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维肌卫星细胞 / 干细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质 ( 胶原, 多糖, 糖蛋白 )

51 Stem cells in skeletal muscle Muscle stem cells Muscle satellite cell 肌卫星细胞 Tendon stem/progenitor cells 肌腱干细胞 MSC 间充质干细胞 EPC 血管内皮祖细胞 ECM niche

Stem cells in muscles and repair Muscle stem cells Muscle satellite cell Resident mononuclear stem cells Intimately associated with the myofibers Sitting tightly in grooves on the myofiber surface

52 Stem cells in muscles and repair Muscle stem cells Muscle satellite cell Resident mononuclear stem cells Intimately associated with the myofibers Sitting tightly in grooves on the myofiber surface receive and respond to signals coming from their partner myofibers Muscle satellite cell PNAS 2007 Main driver of endogenous skeletal muscle repair Identified by their tissue localization and their expression of a panel of molecular markers including Pax7, CXCR4, b1-integrin, and CD34 (Sherwoodet al. 2004). Repaired muscle

53 Stem Cells in tendon Tendon stem/progenitor cells (Nat Med, 2007) MSC like Multipotential Self-renew May involve in tendon repair Tenocytes Mature fibroblast form tendon No specific markers for tendon stem cells and tenocytes hinder to clarify tendon biology and regeneration mechanism

54 ECM in muscles and tendon Collagen: connect tissues and transfer mechanical stress Main ECM of muscles and tendon Type I, III, V, XIV

55 课程设置 -- 骨骼肌课程内容总论 : 人体的重要骨骼肌分布分类和生物力学模型一肌肉的构造与各部分的功能 : 肌腹肌腱神经血管, 筋膜二肌肉的组织成分与功能 : 细胞 ( 肌肉细胞 / 肌纤维卫星细胞间质干细胞血管内皮细胞, 肌腱细胞, 肌腱干细胞 ) 细胞外基质( 胶原, 多糖, 糖蛋白 ) 三肌肉的收缩机制和功能四肌肉肌腱营养生长维持和愈合过程

56 肌肉营养生长维持和愈合过程 1. 肌肉发育 2. 肌肉损伤修复过程及目前存在的问题

57 Schematic representation of somitogenesis. (From: J Anat. 2003)

58 Skeletal muscle formation in the limb(from: J Anat. 2003)

59 Stages of muscle development

Repair of adult skeletal muscles 1. specialized immune cells, called macrophagesmove to the injured area, cleaning up and removing the damaged muscle fibers. 2.

60 Repair of adult skeletal muscles 1. specialized immune cells, called macrophagesmove to the injured area, cleaning up and removing the damaged muscle fibers. 2. blood vessels delivering oxygen and other nutrients necessary for muscle repair. 3. Satellite being activated - fusing together, to regenerate a new muscle fiber 4. New healed muscle fibers steps of muscle repair and healing

61 Repair of adult skeletal muscles Muscle stem cells Satellite cells Muscles stem cells in muscle repair

62 Repair of adult skeletal muscles Muscles stem cells division and proliferation

63 Problem remaining Large defect cannot be repaired Aging cannot be reversed Atrophy What about stem cells in these area? Differentiation Isolation

64 elife 杜克大学的研究人员在实验室中成功培育出人骨骼肌, 它们能够像自然组织那样收缩和响应外部刺激, 例如电脉冲生化信号和药物这些实验室培育的组织, 不久就能允许研究人员在体外的功能性人肌肉中测试新药和研究疾病

65 New research on muscle stem cells: epigenetics affect aging and repair (Cell reports 2013) How aging affect your muscles? Why stem cells different from mature cells. Why aging affect your stem cells?

66 Gene changing during muscle stem cells aging and repair Aging Repair muscle stem cells

67 Epigenetics changing in Muscle stem cells aging Histone changing in aging Do you know what is Epigenetics? How about genetics??

68 The level of H3K27me3 was low in QSCs(aging cells) and dramatically increased in ASCs

69 Epigenetics changing in Muscle stem cells aging and regeneration Epigenetic changes accumulate and may lead to a functional decline in quiescent stem cells

70 Control muscle stem cells migration for regeneration and anti atrophy 一种名为 ephrin 的几个亚型对卫星细胞有效, 细胞一接触到 ephrin 制造的条纹, 就会立刻转弯, 改变行进方向干细胞的运动就像让一个人蒙住眼睛在过道上走, 他们会通过触摸墙壁来感知路径而长长的平行的肌纤维表面有这些 ephirin, 从而能帮助卫星细胞沿着更直线的方向到达发来求救信号的远处 Ephrin 条纹给卫星细胞以不同的信号, 能让它们平行排列形成肌纤维, 从卫星细胞离开干细胞群, 分布到所有的肌肉, 到最后形成有组织且纹理清晰的新纤维, 这些步骤必不可少

71 干细胞培养大块肌肉 For eat 2011 年, 荷兰科学家宣称可在体外培养肌肉组织, 5 万美元一顿 Will you eat it???? For regeneration

72 Tissue regeneration 五角大楼三军再生医学研究所身体部位肌肉损失至少达到 25%( 被研究人员称之为大量损失 ) 或者需要接受截肢手术的现役士兵和老兵匹兹堡大学的研究小组利用猪细胞为士兵再生肌肉在首次进行临床试验后短短几个月, 他们已经为 4 名士兵进行了手术, 临床试验将在 24 个月内结束, 这项技术将成为整形外科医生和外伤外科医生的一种标准疗法

73 Stem cells therapy and repair in animal model 2008, 波士顿乔士林糖尿病中心 Amy J. Wagers 在 Cell 首先报道肌肉干细胞可修复小鼠肌萎缩模型证明干细胞用于治疗退行性肌肉疾病 2010 年, 在 SCIENCE 子刊报道腿部肌肉受伤的年轻实验鼠为研究对象发现, 植入肌肉干细胞可以使实验鼠肌肉恢复得比受伤前更强大, 还可帮助实验鼠抵御因衰老而导致的肌肉萎缩干细胞移植可助实验鼠受伤肌肉恢复且产生搞衰老能力, 维持终身 (1 year)

74 Muscle differentiation

75 肌腱生长维持和愈合过程 1. 肌腱发育过程 2. 肌腱成熟过程 3. 肌腱损伤修复过程及目前存在的问题

76 Tendon development Tissue interactions required for tendon progenitor induction in vertebrate embryos.

77 Tendon development The main stages and regulators of tendon induction and differentiation in vertebrate embryos.(devlopment 2011)

78 Tendon maturation: cell collagen 0d 1d 2.5d 4d 7d 14d 28d 56d Rat tendon maturation (provided by Prof. OuyangHong Wei 欧阳宏伟 )

79 Tendon maturation: collagen maturation 4d 1d 14d 7d 28d 10d 56d Rat tendon maturation (provided by Prof. Ouyang Hong Wei)

80 Tendon injury: 肌腱损伤对于运动员而言可能意味着运动生涯的结束 Especially common (in USA) 1.Shoulder s rotator cuff tendons (51,000 /year) 2.Achilles tendon (44,000/year) 3.Patellar tendon (42,000/year) 4.Anterior cruciate ligament (over 200,000 /year) 肌腱断裂 Rafael Nadal: 慢性髌腱炎

Tendon rupture and repair: current therapy Autografts Allograft gold standard, avoid rejection Additional surgery, lack of resource Allografts and Xenografts Primarily

81 Tendon rupture and repair: current therapy Autografts Allograft gold standard, avoid rejection Additional surgery, lack of resource Allografts and Xenografts Primarily type I collagen Tendons, dermal, pericardium, SIS-ECM Transmit disease Immunogenic response Decellularized allografts and Xenografts 2016 年 10 月 10 日星期一 1 时 27 分 57 秒 81

82 浙江大学干细胞与组织工程中心研究进展

83 进展一 : 肌腱分化 (ESC 来源肌腱诱导内源性肌腱修复 ) 利用 hesc 在动物体内构建组织工程肌腱并探明干细胞在肌腱修复再生中发挥的功能胚胎肌腱基质生长分化因子 ESC 来源组织工程肌腱分泌胚胎肌腱基质和生长分化因子 Stem Cells

84 进展二 : 肌腱分化 ( 转录因子与力学协同调控 ) 力学刺激和转录因子 scleraxis(scx) 协同调控干细胞腱系分化激活肌腱系分化转录因子力学刺激阻止骨软骨系分化 84

85 肌腱炎临床治疗自体细胞因子治疗肌腱末端病典型临床病例典型病例 1: 张 **, 女, 女篮运动员,19 岁, 髌骨尖疼痛, 右膝关节肿痛, 屈曲活动受限半年治疗 2 周后症状明显缓解现已恢复训练典型病例 2: 徐 *, 男,20 岁, 拳击运动员, 右踝关节周围疼痛, 左肘关节内侧疼痛半年, 治疗 2 周后症状明显缓解

86 Adult Tendon repair: big challenge never regeneration

87 Skeletal muscle injury and reconstruction Stem cells and regenerative medicine Tissue engineering Tendon regeneration

88 What kind of tissue engineering?

89 Stem cells and tissue engineering Milestone of tissue engineering

90 Thank you for your attention

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$(Microsoft PowerPoint - \271\307\367\300\274\241)$ 人体结构与功能学 Human Anatomy and Physiology Skeletal Muscle Tissue 骨骼肌陈晓 Chenxiao.610@gmail.com 浙江大学医学院干细胞与组织工程中心人类所有改造世界改造自己的意识活动都需要通过骨骼肌运动实现课程设置 -- 骨骼肌理论课程内容,2.5 学时课程目标 : 能分析大关节运动时肌肉力学模式从肌肉肌腱组织结构分析损伤时修复的策略