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궁둥신경절단이흰쥐장딴지근에미치는영향

The Effects of Sciatic Neurectomy on Rat Gastrocnemius Muscle

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참고문헌

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주제분류해부학

초록

근육위축은 신경절단이나 부동, 고정, 비운동, 비부하 등에 의해 유발될 수 있다. 본 연구는 신경절단 후 일어나는 근육 손상의 기전을 이해하고자 시행되었다. 흰쥐 왼궁둥신경을 절단한 후 8주에 양쪽 장딴지근의 형태학적 변화를 광학 및 전자현미경으로 관찰하였고, Western blot 분석을 통해 근육발육과 관련된 단백질의 발현정도를 측정하였다. 궁둥신경이 절단된 왼쪽 다리의 장딴지근의 무게는 유의하게 감소되었다. 광학현미경상에서 신경절단에 의해 근육섬유의 직경과 가로면의 면적이 정상대조군에 비하여 현저하게 감소하였다. 장딴지근에서 아교섬유가 신경절 단 후 증가되었다. 전자현미경상에서 신경절단에 따른 근육섬유의 변화는 주로 근원섬유의 손상과 소실, 사립체의 손상과 소실, 가로세관 및 근육형질세망의 소실 등이었다. 근육원섬유의 직경이 작아지고, 근육원섬유의 구성성분 인 굵은 및 가는 근육미세섬유의 수가 현저하게 감소하였으며 이들의 배열이 매우 불규칙하였다. 근육원섬유마디 에서 끝가로막의 소실이 근육미세섬유의 소실보다 더 많았고, 가는근육미세섬유의 소실이 굵은근육미세섬유보다 더 심했다. 근육섬유의 핵은 퍼진염색질과 약한 뭉친염색질을 보였으며, 간혹 핵소체도 관찰되었다. 사립체의 손상 은 주로 농축과 팽대 및 사립체능선의 소실 등이었다. 가로세관이나 근육형질세망은 그 수가 감소하였으며, 근육 형질내에 무정형의 물질들과 함께 불규칙하게 흩어져 있었다. 결합조직내에서 간혹 근육위성세포가 근육섬유와 인접하여 관찰되었으며, 형태학적으로 비활성상태였다. 근육섬유의 발육관련 인자인 MyoD와 myogenin은 현저하 게 감소하였고, 세포의 성장과 증식에 관련된 인자인 인산화 mTOR와 FOXO1도 감소하였다. 반면에 세포위축관 련인자인 MuRF1은 현저하게 증가하였다. 이상의 결과는 신경절단에 의한 장딴지근의 형태학적 변화는 근육섬유의 발육을 유지하는 단백형성의 감소와 단백파괴의 증가에 의한 근육미세섬유와 세포소기관의 소실에 따른 세포위축에 기인하는 것으로 추측된다.

Abstract

The effects of unilateral sciatic neurectomy on gastrocnemius muscle were studied in adult male rats. The morphological changes of both gastrocnemius muscles were observed by light and electron microscopy. Western blot analysis was performed to study the protein expression. Following the denervation, the affected muscle weights decreased significantly than normal. And the denervation led to a significant reduction in the area and diameter of muscle fibers on light microscopy. The affected muscle fibers showed the decreasing in size and the irregularity of myofibrilar arrangement on electron microscopy. On transverse view, the area of affected muscle fibers were smaller than normal. Their myofibrils were smaller and very irregular in size. The thin and thick myofilaments were not regular and partially lost. Mitochondria between myofibrils and subsarcolemmal were mostly lost and irregular. Some satellite cells were observed adjacent the muscle fiber, but they were inactive morphologically. On longitudinal view, most of myofibrils in affected muscle fibers were lost generally or partially although the their most sarcomeres were regularly arranged. Z line and myofilaments were lost partially and were partially irregularly arranged. The loss of thin myofilaments was more than that of thick myofilaments. Much debris of cell organelles were scattered among myofibrils. The expression of MyoD and myogenin were decrease significantly and the expression of p-mTOR and p-FOXO1 were decreased, too. On the other hand, MuRF1 was increased significantly. Taken together, the main effect of gastrocnemius muscle by sciatic neurectomy is the atrophy as a result of the loss of myofilaments and cell organelles through the decrease of protein synthesis and the increase of protein degradation.

참고문헌 (52)

  1. Al-Amood WS, "A comparison of the effects of denervation on the mechanical properties of rat and guineapig skeletal muscle", J Physiol, 414, pp.1~16 (1989)
  2. Batt J, "Bain J", FASEB J, 20, pp.115~117 (2006)
  3. Bodine SC, "Akt", mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo, 2001, pp.3, 1014~1019
  4. Borisov AB, "Cell death in denervated skeletal muscle is distinct from classical apoptosis", Anat Rec, 258, pp.305~318 (2000)
  5. Borisov AB, "Remodeling of the vascular bed and progressive loss of capillaries in denervated skeletal muscle", Anat Rec, 258, pp.292~304 (2000)
  6. Borisov AB, "Progressive microvascular insufficiency in long-term denervated skeletal muscle", FASEB J, 10, pp.533~ (1996)
  7. Buonanno A, "The MyoD family of myogenic factors is regu-lated by electrical activity: isolation and characterization of a mouse Myf-5 cDNA", Nucleic Acids Res, 20, pp.539~544 (1992)
  8. Burnett PE, "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1", Proc Natl Acad Sci USA, 통권 : 95, pp.1432~1437 (1998)
  9. Carlson BM, "Studies on the regenerative recovery of long-term denervated muscle in rats", Restor Neurol Neurosci, 10, pp.77~84 (1996)
  10. Carlson CJ, "Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading", Am J Physiol, 277, pp.601~606 (1999)
  11. Cohn RD, "Molecular basis of muscular dystrophies", Muscle Nerve, 23, pp.1456~1471 (2000)
  12. Dupont Salter AC, "Effects of muscle immobilization at Eifferent lengths on tetrodotoxininduced disuse atrophy", IEEE Trans Neural Syst Rehabil Eng, 1, pp.209~217 (2003)
  13. Eftimie R, "Myogenin and MyoD join a family of skeletal muscle genes regulated by electricalactivity", Proc Natl Acad Sci USA, 통권 : 88, pp.1349~1353 (1991)
  14. Gutmann E, "Morphological changes in the denervated muscle, In The denervated muscle", Publishing House of Czechoslovak Academy of Science, pp.57~102 (1962)
  15. Hara K, "Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism", J Biol Chem, 273, pp.14484~14494 (1998)
  16. Hawke TJ, "Myogenic satellite cells: physiology to molecular biology", J Appl Physil, 91, pp.534~551 (2001)
  17. Hnik P, "Rate of denervation muscle atrophy, In The denervated muscle", pp.341~371 (1962), Publishing House of Czechoslovak Academy of Science
  18. Hoppeler H, "Recommendations for muscle research in space", Int J Sports Med, 4, pp.280~282 (1997)
  19. Hyatt JP, "Nerve activity independent regulation of skeletal muscle atrophy role of MyoD and myogenin in satellite cells and myonuclei", Am J Physiol Cell Physiol, 285, pp.1161~1173 (2003)
  20. Hyatt JP, "Activity-unrelated neural control of myogenic factors in a slow muscle", Muscle Nerve, 33, pp.49~60 (2006)
  21. Jackman RW, "The molecular basis of skeletal muscle atrophy", Am J Physiol Cell Physiol, 287, pp.834~843 (2004)
  22. Jejurikar SS, "Satellite cell depletion in degenerative skeletal muscle", Apoptosis, 8, pp.573~578 (2003)
  23. Kamei Y, "Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, downregulated Type I (slow twitch", red muscle) fiber genes, and impaired glycemic control, 2004, pp.279, 41114~41123
  24. Karnovsky MT, "A formalehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy", J Cell Biol, 27, pp.137~ (1965)
  25. Kedar V, "Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I", Proc Natl Acad Sci USA, 통권 : 52, pp.18135~18140 (2004)
  26. Kreuzer F, "Oxygen transfer form blood to mitochondria, In The lung: scientific foundations", pp.1913~1923 (1997), Lippincott-Raven
  27. Lee SW, "Regulation of muscle protein degradation: Coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase", J Am Soc Nephrol, 15, pp.1537~1545 (2004)
  28. Leger B, "Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy", J Physiol, 576, pp.923~933 (2006)
  29. Lu DX, "Electron microscopic study of long-term denervated rat skeletal muscle", Anat Rec, 248, pp.355~365 (1997)
  30. Luft JH, "Improvement in epoxy resin embedding methods", J Biophys Biochem Cyto, 9, pp.409~412 (1961)
  31. McGeachie J, "Cell proliferation in skeletal muscle following denervation or tenoromy", Cell Tissue Res, 193, pp.259~267 (1978)
  32. Murray, MA, "Cell proliferation in denervated muscle: Time course, distribution and relation to disuse", Neuroscience, 7, pp.1817~1822 (1982)
  33. Murray MA, "Cell proliferation in enervated muscle: Identity and origin of dividing cells", Neuroscience, 7, pp.1823~1833 (1982)
  34. Oki S, "Endothelial pores in the rat soleus muscle capillaries after experimental limb immobilization", J Electron Microsc, 45, pp.314~316 (1996)
  35. Oki S, "Capillary changes with fenestrations in the contralateral soleus muscle of the rat following unilateral limb immobilization", J Orthop Sci, 4, pp.28~31 (1999)
  36. Pallafacchina G, "A protein kinase B-dependent and rapamycinsensitive pathway controls skeletal muscle growth but not fiber type specification", Proc Natl Acad Sci USA, 통권 : 99, pp.9213~9218 (2002)
  37. Reznick AZ, "Expression of matrix metalloproteinase, inhibitor, and acid phosphatase in muscles of immobilized hindlimbs of rats", Muscle Nerve, 27, pp.51~59 (2003)
  38. Riley DA, "Skeletal muscle fiber atrophy: altered thin filament density changes slow fiber force and shortening velocity", Am J Physiol Cell Physiol, 288, pp.360~365 (2005)
  39. Riley DA, "Disproportionate loss of thin filaments in human soleus muscle after 17-day bed rest", Muscle Nerve, 21, pp.1280~1289 (1998)
  40. Robert WJ, "The molecular basis of skeletal muscle atrophy", Am J Physiol Cell Physiol, 287, pp.834~843 (2003)
  41. Rommel C, "Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K", Akt, Akt, pp.GSK3 pathways, Nat Cell Biol[DOI]
  42. Rommel C, "Differentiation stage-specific inhibition of the raf-MEKERK pathway by Akt", Science, 286, pp.1738~1741 (1999)
  43. Russo TL, "Electrical stimulation based on chronaxie reduces atrogin-1 and myoD gene expressions in denervated rat muscle", Muscle Nerve, 35, pp.87~97 (2007)
  44. Sakuma K, "The adaptive response of MyoD family proteins in overloaded, regenerating and denervated rat muscles", Biochim Biophys Acta, 1428, pp.284~292 (1999)
  45. Sandri M, "Foxo transcription factors induce the atrophyrelated ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy", Cell, 117, pp.399~412 (2004)
  46. Stitt TN, "The IGF-1", PI3K, Mol Cell, pp.2004, 14[DOI]
  47. Sun HL, "Lower Limb Wrapping Prevents Hypotension, but Not Hypothermia or Shivering, After the Introduction of Epidural Anesthesia for Cesarean Delivery", Anesth Analg, 99, pp.241~244 (2004)
  48. Takala TE, "Biochemical composition of muscle extracellular marix: the effect of loading", Scand J Med Sci Sports, 10, pp.321~325 (2000)
  49. Tyml K, "Differential microvascular response to disuse in rat hindlimb skeletal muscles", J Appl Physiol, 87, pp.1496~1505 (1999)
  50. Viguie CA, "Quantitative study of the effects of long-term denervation on the extensor digitorum longus muscle of rat", Anat Rec, 248, pp.346~354 (1997)
  51. William W, "Tenotomy decreases reporter protein synthesis via the 3 -myosin heavy chain mRNA", Am J Physiol Cell Physiol, 279, pp.257~265 (2000)
  52. Zhou MY, "Myosin heavy chain isoforms of human muscle after short-term spaceflight", J Appl Physiol, 78, pp.1740~1744 (1995)

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