體外震波治療對糖尿病大鼠慢性創面愈合及組織學影響_《中國修復重建外科雜志》

作者：

燕曉宇 , 楊光 , 成亮 , 陳明 , 程相國 , 柴益民 , 羅從風 , 曾炳芳

上海交通大學附屬第六人民醫院骨科（上海，200233）;

關鍵詞：

體外震波糖尿病慢性創面血管新生創面愈合大鼠

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目的體外震波（extracorporeal shock wave，ESW）可促進血管新生和組織修復，通過觀察低能量ESW治療糖尿病大鼠慢性創面的效果，探討其促進糖尿病慢性創面愈合的機制。方法6～8周齡雄性SD大鼠96只，體重（220 ± 20）g，隨機分為3組（糖尿病對照組、ESW治療組及正常對照組），每組32只。取糖尿病對照組、ESW治療組大鼠，腹腔注射鏈脲佐菌素（60 mg/kg）制備糖尿病大鼠模型后，于背部制備1個直徑1.8 cm的圓形皮膚全層創面，建立糖尿病大鼠慢性創面模型。正常對照組大鼠同法制備創面。創面制備后1 d ESW治療組采用0.11 mJ/mm2、1.5 Hz的ESW對創面干預500脈沖；糖尿病對照組及正常對照組創面未行ESW治療。觀察創面愈合情況；于3、7、14 d取創面組織行HE及Masson染色，觀察創面組織學變化；行CD31和增殖細胞核抗原（proliferating cell nuclear antigen，PCNA）免疫組織化學染色，觀察創面細胞增殖及血管化程度。結果糖尿病對照組創面閉合率低于正常對照組，創面閉合時間延長（P lt; 0.05），治療后3、7、14 d，創面組織炎性細胞浸潤明顯，膠原纖維相對面積密度、創面微血管密度、PCNA陽性細胞相對密度均低于正常對照組（P lt; 0.05）。ESW治療組與糖尿病對照組相比，創面愈合時間縮短，創面閉合率提高（P lt; 0.05），各時間點炎性細胞計數減少，肉芽組織生長良好，創面內膠原纖維相對面積密度、微血管密度和PCNA陽性細胞相對密度增加，差異有統計學意義（P lt; 0.05）；ESW治療組與正常對照組相比，微血管密度和PCNA陽性細胞相對密度差異均無統計學意義（P gt; 0.05）。結論低能量ESW治療可以抑制糖尿病大鼠慢性創面內局部炎性反應，提高創面內修復細胞增殖能力，增加微血管形成和膠原沉積，使肉芽組織形成增加，最終促進創面愈合。

引用本文： 燕曉宇,楊光,成亮,陳明,程相國,柴益民,羅從風,曾炳芳. 體外震波治療對糖尿病大鼠慢性創面愈合及組織學影響. 中國修復重建外科雜志, 2012, 26(8): 961-967. doi: 復制

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2.	Chao YH, Tsuang YH, Sun JS, et al. Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism. Ultrasound Med Biol, 2008, 34(5): 841-852.
3.	Speed CA. Extracorporeal shock-wave therapy in the management of chronic soft-tissue conditions. J Bone Joint Surg (Br), 2004, 86(2): 165-171.
4.	燕曉宇, 曾炳芳, 柴益民, 等. 低能量體外震波擴大隨意皮瓣成活面積的實驗研究. 中華顯微外科雜志, 2008, 31(1): 43-46.
5.	Kuo YR, Wang CT, Wang FS, et al. Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes. Wound Repair Regen, 2009, 17(4): 522-530.
6.	Qureshi AA, Ross KM, Ogawa R, et al. Shock wave therapy in wound healing. Plast Reconstr Surg, 2011, 128(6): 721e-727e.
7.	Wang CJ, Kuo YR, Wu RW, et al. Extracorporeal shockwave treatment for chronic diabetic foot ulcers. J Surg Res, 2009, 152(1): 96-103.
8.	Wang CJ, Wu RW, Yang YJ. Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. Diabetes Res Clin Pract, 2011, 92(2): 187-193.
9.	Moretti B, Notarnicola A, Maggio G, et al. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy. BMC Musculoskelet Disord, 2009, 10: 54.
10.	Saggini R, Figus A, Troccola A, et al. Extracorporeal shock wave therapy for management of chronic ulcers in the lower extremities. Ultrasound Med Biol, 2008, 34(8): 1261-1271.
11.	Zins SR, Amare MF, Tadaki DK, et al. Comparative analysis of angiogenic gene expression in normal and impaired wound healing in diabetic mice: effects of extracorporeal shock wave therapy. Angiogenesis, 2010, 13(4): 293-304.
12.	Yang G, Luo C, Yan X, et al. Extracorporeal shock wave treatment improves incisional wound healing in diabetic rats. Tohoku J Exp Med, 2011, 225(4): 285-292.
13.	Junod A, Lambert AE, Stauffacher W, et al. Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest, 1969, 48(11): 2129-2139.
14.	Chao CY, Cheing GL. Microvascular dysfunction in diabetic foot disease and ulceration. Diabetes Metab Res Rev, 2009, 25(7): 604-614.
15.	Laing T, Hanson R, Chan F, et al. The role of endothelial dysfunction in the pathogenesis of impaired diabetic wound healing: a novel therapeutic target? Med Hypotheses, 2007, 69(5): 1029-1031.
16.	Yavuz D, Tu?tepe H, Cetinel S, et al. Collagen ultrastructure and TGF-beta1 expression preserved with aminoguanidine during wound healing in diabetic rats. Endocrine research, 2005, 31(3): 229-243.
17.	Black E, Vibe-Petersen J, Jorgensen LN, et al. Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control. Arch Surg, 2003, 138(1): 34-40.
18.	Bermudez DM, Herdrich BJ, Xu J, et al. Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications. Am J Pathol, 2011, 178(5): 2215-2223.
19.	Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol, 2007, 25(1): 9-18.
20.	Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest, 2007, 117(5): 1219-1222.
21.	Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg, 1998, 176(2A Suppl): 26S-38S.
22.	Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res, 2009, 37(5): 1528-1542.
23.	Kalra B, Kalra S, Chatley G, et al. Rat bite as a cause of diabetic foot ulcer—a series of eight cases. Diabetologia, 2006, 49(6): 1452-1453.
24.	田曉紅, 柏樹令, 田偉, 等. 表皮干細胞在糖尿病創面愈合過程中的動態變化. 中國修復重建外科雜志, 2007, 21(7): 693-697.
25.	Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev, 2003, 23(2): 117-145.
26.	Roy H, Bhardwaj S, Yla-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett, 2006, 580(12): 2879-2887.
27.	Vetrano M, d’Alessandro F, Torrisi MR, et al. Extracorporeal shock wave therapy promotes cell proliferation and collagen synthesis of primary cultured human tenocytes. Knee Surg Sports Traumatol Arthrosc, 2011, 19(12): 2159-2168.
28.	Wang FS, Wang CJ, Sheen-Chen SM, et al. Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. J Biol Chem, 2002, 277(13): 10931-10937.
29.	Nurzynska D, Di Meglio F, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol, 2008, 34(2): 334-342.
30.	Yu TC, Liu Y, Tan Y, et al. Shock waves increase T-cell proliferation or IL-2 expression by activating p38 MAP kinase. Acta Biochim Biophys Sin, 2004, 36(11): 741-748.

1. Fard AS, Esmaelzadeh M, Larijani B. Assessment and treatment of diabetic foot ulcer. Int J Clin Pract, 2007, 61(11): 1931-1938.
2. Chao YH, Tsuang YH, Sun JS, et al. Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism. Ultrasound Med Biol, 2008, 34(5): 841-852.
3. Speed CA. Extracorporeal shock-wave therapy in the management of chronic soft-tissue conditions. J Bone Joint Surg (Br), 2004, 86(2): 165-171.
4. 燕曉宇, 曾炳芳, 柴益民, 等. 低能量體外震波擴大隨意皮瓣成活面積的實驗研究. 中華顯微外科雜志, 2008, 31(1): 43-46.
5. Kuo YR, Wang CT, Wang FS, et al. Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes. Wound Repair Regen, 2009, 17(4): 522-530.
6. Qureshi AA, Ross KM, Ogawa R, et al. Shock wave therapy in wound healing. Plast Reconstr Surg, 2011, 128(6): 721e-727e.
7. Wang CJ, Kuo YR, Wu RW, et al. Extracorporeal shockwave treatment for chronic diabetic foot ulcers. J Surg Res, 2009, 152(1): 96-103.
8. Wang CJ, Wu RW, Yang YJ. Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. Diabetes Res Clin Pract, 2011, 92(2): 187-193.
9. Moretti B, Notarnicola A, Maggio G, et al. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy. BMC Musculoskelet Disord, 2009, 10: 54.
10. Saggini R, Figus A, Troccola A, et al. Extracorporeal shock wave therapy for management of chronic ulcers in the lower extremities. Ultrasound Med Biol, 2008, 34(8): 1261-1271.
11. Zins SR, Amare MF, Tadaki DK, et al. Comparative analysis of angiogenic gene expression in normal and impaired wound healing in diabetic mice: effects of extracorporeal shock wave therapy. Angiogenesis, 2010, 13(4): 293-304.
12. Yang G, Luo C, Yan X, et al. Extracorporeal shock wave treatment improves incisional wound healing in diabetic rats. Tohoku J Exp Med, 2011, 225(4): 285-292.
13. Junod A, Lambert AE, Stauffacher W, et al. Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest, 1969, 48(11): 2129-2139.
14. Chao CY, Cheing GL. Microvascular dysfunction in diabetic foot disease and ulceration. Diabetes Metab Res Rev, 2009, 25(7): 604-614.
15. Laing T, Hanson R, Chan F, et al. The role of endothelial dysfunction in the pathogenesis of impaired diabetic wound healing: a novel therapeutic target? Med Hypotheses, 2007, 69(5): 1029-1031.
16. Yavuz D, Tu?tepe H, Cetinel S, et al. Collagen ultrastructure and TGF-beta1 expression preserved with aminoguanidine during wound healing in diabetic rats. Endocrine research, 2005, 31(3): 229-243.
17. Black E, Vibe-Petersen J, Jorgensen LN, et al. Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control. Arch Surg, 2003, 138(1): 34-40.
18. Bermudez DM, Herdrich BJ, Xu J, et al. Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications. Am J Pathol, 2011, 178(5): 2215-2223.
19. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol, 2007, 25(1): 9-18.
20. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest, 2007, 117(5): 1219-1222.
21. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg, 1998, 176(2A Suppl): 26S-38S.
22. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res, 2009, 37(5): 1528-1542.
23. Kalra B, Kalra S, Chatley G, et al. Rat bite as a cause of diabetic foot ulcer—a series of eight cases. Diabetologia, 2006, 49(6): 1452-1453.
24. 田曉紅, 柏樹令, 田偉, 等. 表皮干細胞在糖尿病創面愈合過程中的動態變化. 中國修復重建外科雜志, 2007, 21(7): 693-697.
25. Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev, 2003, 23(2): 117-145.
26. Roy H, Bhardwaj S, Yla-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett, 2006, 580(12): 2879-2887.
27. Vetrano M, d’Alessandro F, Torrisi MR, et al. Extracorporeal shock wave therapy promotes cell proliferation and collagen synthesis of primary cultured human tenocytes. Knee Surg Sports Traumatol Arthrosc, 2011, 19(12): 2159-2168.
28. Wang FS, Wang CJ, Sheen-Chen SM, et al. Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. J Biol Chem, 2002, 277(13): 10931-10937.
29. Nurzynska D, Di Meglio F, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol, 2008, 34(2): 334-342.
30. Yu TC, Liu Y, Tan Y, et al. Shock waves increase T-cell proliferation or IL-2 expression by activating p38 MAP kinase. Acta Biochim Biophys Sin, 2004, 36(11): 741-748.

《中國修復重建外科雜志》

體外震波治療對糖尿病大鼠慢性創面愈合及組織學影響

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《中國修復重建外科雜志》

體外震波治療對糖尿病大鼠慢性創面愈合及組織學影響

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