• 山西醫(yī)科大學(xué)第二附屬醫(yī)院骨科（太原，030001）;

目的 研究川芎嗪對失神經(jīng)骨骼肌萎縮中FoXO3a、MAFbx 及MuRF1 表達(dá)的影響。 方法 8 周齡雌性SD 大鼠54 只，體重（200 ± 10） g。隨機(jī)分為3 組，即正常對照組（A 組，n=6）、失神經(jīng)對照組（B 組，n=24）、干預(yù)組（C組，n=24）。B、C 組實驗動物制備右下肢失神經(jīng)腓腸肌動物模型，C 組于模型制備后每日腹腔注射川芎嗪注射液80 mg/（kg·d），B 組每日腹腔注射等劑量生理鹽水；A 組實驗動物不作任何處理。取A 組實驗動物以及造模后2、7、14、28 d B、C 組實驗動物各6 只，處死取其雙側(cè)腓腸肌稱濕重，計算腓腸肌肌濕重比；另取右側(cè)肌組織采用RT-PCR 及Western blot檢測各時間點(diǎn)FoXO3a、MAFbx、MuRF1 mRNA 和蛋白表達(dá)水平。 結(jié)果 與A 組比較，隨著大鼠失神經(jīng)時間延長，B、C 組腓腸肌肌濕重比逐漸下降，差異均有統(tǒng)計學(xué)意義（P  lt; 0.05）；造模后7、14、28 d，C 組腓腸肌肌濕重比高于B 組，且差異有統(tǒng)計學(xué)意義（P  lt; 0.05）。B、C 組造模后7、14、28 d，F(xiàn)oXO3a、MAFbx、MuRF1 mRNA 和蛋白表達(dá)水平均較A 組高，C 組各時間點(diǎn)均較B 組降低，差異均有統(tǒng)計學(xué)意義（P  lt; 0.05）。 結(jié)論 川芎嗪可能通過降低FoXO3a、MAFbx 以及MuRF1 mRNA 和蛋白表達(dá)水平進(jìn)而延緩失神經(jīng)骨骼肌萎縮。

引用本文： 王紅兵,梁炳生,彭春輝,王鵬飛. 川芎嗪對失神經(jīng)骨骼肌萎縮大鼠FoXO3a、MAFbx以及MuRF1 表達(dá)的影響. 中國修復(fù)重建外科雜志, 2012, 26(5): 597-600. doi: 復(fù)制

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2. Zhao J, Brault JJ, Schild A, et al. Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy, 2008, 4(3): 378-380.
3. Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy, 2008, 4(4): 524-526.
4. 劉安唐, 江華. MAFbx/Atrogin-1和MuRF1在大鼠肌肉游離移植模型中的表達(dá)和意義. 上海: 第二軍醫(yī)大學(xué), 2007.
5. Jones A, Hwang DJ, Narayanan R, et al. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology, 2010, 151(8): 3706-3719.
6. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal Muscle Atrophy. Science, 2001, 294(5547): 1704-1708.
7. Chen YW, Gregory CM, Scarborough MT, et al. Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics, 2007, 31(3): 510-520.
8. Dehoux M, Van Beneden R, Pasko N, et al. Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology, 2004, 145(11): 4806-4812.
9. Dehoux MJ, van Beneden RP, Fernández-Celemín L, et al. Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett, 2003, 544(1-3): 214-217.
10. Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol, 2007, 292(1): C188-C199.
11. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004, 117(3): 399-412.
12. Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol, 2010, 298(1): C38-C45.
13. Sandri M, Lin J, Handschin C, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A, 2006, 103(44): 16260-16265.
14. Asensio-Pinilla E, Udina E, Jaramillo J, et al. Electrical stimulation combined with exercise increase axonal regeneration after peripheral nerve injury, Exp Neurol, 2009, 219(1): 258-265.
15. Dong F, Hua Y, Zhao P, et al. Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J Nutr Biochem, 2009, 20(12): 992-999.
16. Jin B, Li YP. Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. J Cell Biochem, 2007, 100(4): 960-969.
17. 秦雯. 當(dāng)歸和川芎對尾部懸吊大鼠比目魚肌的影響及其機(jī)制研究. 西安: 西北大學(xué), 2008.
18. 高云芳, 樊小力, 何志仙, 等. 川芎嗪和黃芪對尾部懸吊大鼠比目魚肌肌球蛋白ATP酶活性及肌萎縮的影響. 航天醫(yī)學(xué)與醫(yī)學(xué)工程, 2005, 18(4): 262-266.
19. 曹晉, 高云芳, 劉坤. 川芎及兩種主要藥效成分對廢用性肌萎縮的影響. 中國應(yīng)用生理學(xué)雜志, 2010, 26(1): 109-113.
20. de Palma L, Marinelli M, Pavan M, et al. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine, 2008, 75(1): 53-57.
21. Yoshida T, Semprun-Prieto L, Sukhanov S, et al. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol, 2010, 298(5): H1565-H1570.
22. Doucet M, Russell AP, Léger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 176(3): 261-269.
23. Mcelhinny AS, Kakinuma K, Sorimachi H, et al. Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and May have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol, 2002, 157(1): 125-136.
24. Witt CC, Witt SH, Lerche S, et al. Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J, 2008, 27(2): 350-360.
25. Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A, 2001, 98(25): 14440-14445.
26. Poylin V, Fareed MU, O’Neal P, et al. The NF-κB inhibitor curcumin blocks Sepsis-Induced muscle proteolysis. Mediators Inflamm, 2008, 317851.
27. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 2004, 117(4): 421-426.
28. Sáinz N, Rodríguez A, Catalán V, et al. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One, 2009, 4(9): e6808.
29. 曹晉. 川芎及其主要成分和達(dá)烏爾黃鼠冬眠期抗廢用性肌萎縮的機(jī)制研究. 西安: 西北大學(xué), 2009.
30. 李光月, 高云芳. 川芎嗪抗廢用性肌萎縮藥效作用與作用機(jī)制初步研究. 西安: 西北大學(xué), 2011.
  1. 1. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev, 2002, 82(2): 373-428.
  2. 2. Zhao J, Brault JJ, Schild A, et al. Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy, 2008, 4(3): 378-380.
  3. 3. Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy, 2008, 4(4): 524-526.
  4. 4. 劉安唐, 江華. MAFbx/Atrogin-1和MuRF1在大鼠肌肉游離移植模型中的表達(dá)和意義. 上海: 第二軍醫(yī)大學(xué), 2007.
  5. 5. Jones A, Hwang DJ, Narayanan R, et al. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology, 2010, 151(8): 3706-3719.
  6. 6. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal Muscle Atrophy. Science, 2001, 294(5547): 1704-1708.
  7. 7. Chen YW, Gregory CM, Scarborough MT, et al. Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics, 2007, 31(3): 510-520.
  8. 8. Dehoux M, Van Beneden R, Pasko N, et al. Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology, 2004, 145(11): 4806-4812.
  9. 9. Dehoux MJ, van Beneden RP, Fernández-Celemín L, et al. Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett, 2003, 544(1-3): 214-217.
  10. 10. Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol, 2007, 292(1): C188-C199.
  11. 11. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004, 117(3): 399-412.
  12. 12. Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol, 2010, 298(1): C38-C45.
  13. 13. Sandri M, Lin J, Handschin C, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A, 2006, 103(44): 16260-16265.
  14. 14. Asensio-Pinilla E, Udina E, Jaramillo J, et al. Electrical stimulation combined with exercise increase axonal regeneration after peripheral nerve injury, Exp Neurol, 2009, 219(1): 258-265.
  15. 15. Dong F, Hua Y, Zhao P, et al. Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J Nutr Biochem, 2009, 20(12): 992-999.
  16. 16. Jin B, Li YP. Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. J Cell Biochem, 2007, 100(4): 960-969.
  17. 17. 秦雯. 當(dāng)歸和川芎對尾部懸吊大鼠比目魚肌的影響及其機(jī)制研究. 西安: 西北大學(xué), 2008.
  18. 18. 高云芳, 樊小力, 何志仙, 等. 川芎嗪和黃芪對尾部懸吊大鼠比目魚肌肌球蛋白ATP酶活性及肌萎縮的影響. 航天醫(yī)學(xué)與醫(yī)學(xué)工程, 2005, 18(4): 262-266.
  19. 19. 曹晉, 高云芳, 劉坤. 川芎及兩種主要藥效成分對廢用性肌萎縮的影響. 中國應(yīng)用生理學(xué)雜志, 2010, 26(1): 109-113.
  20. 20. de Palma L, Marinelli M, Pavan M, et al. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine, 2008, 75(1): 53-57.
  21. 21. Yoshida T, Semprun-Prieto L, Sukhanov S, et al. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol, 2010, 298(5): H1565-H1570.
  22. 22. Doucet M, Russell AP, Léger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 176(3): 261-269.
  23. 23. Mcelhinny AS, Kakinuma K, Sorimachi H, et al. Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and May have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol, 2002, 157(1): 125-136.
  24. 24. Witt CC, Witt SH, Lerche S, et al. Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J, 2008, 27(2): 350-360.
  25. 25. Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A, 2001, 98(25): 14440-14445.
  26. 26. Poylin V, Fareed MU, O’Neal P, et al. The NF-κB inhibitor curcumin blocks Sepsis-Induced muscle proteolysis. Mediators Inflamm, 2008, 317851.
  27. 27. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 2004, 117(4): 421-426.
  28. 28. Sáinz N, Rodríguez A, Catalán V, et al. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One, 2009, 4(9): e6808.
  29. 29. 曹晉. 川芎及其主要成分和達(dá)烏爾黃鼠冬眠期抗廢用性肌萎縮的機(jī)制研究. 西安: 西北大學(xué), 2009.
  30. 30. 李光月, 高云芳. 川芎嗪抗廢用性肌萎縮藥效作用與作用機(jī)制初步研究. 西安: 西北大學(xué), 2011.