• 第三軍醫(yī)大學(xué)西南醫(yī)院骨科 全軍矯形外科中心（重慶，400038）;

【摘 要】 目的  肌腱損傷后周?chē)傲邢偎谽2（prostaglandin E2，PGE2）及體外牽伸載荷條件下肌腱細(xì)胞產(chǎn)生的PGE2均升高，通過(guò)觀察外源性PGE2對(duì)兔跟腱膠原含量的影響，探討其與肌腱病發(fā)生的關(guān)系。 方法  取健康3～4月齡日本短耳兔24只，體重2.0～2.5 kg，雌雄不限；根據(jù)PGE2注射劑量不同隨機(jī)分為兩組（n=12）：低劑量組（50 ng）和高劑量組（500 ng）。隨機(jī)選擇一側(cè)后肢跟腱中部經(jīng)皮注射0.2 mL對(duì)應(yīng)劑量PGE2，對(duì)側(cè)對(duì)應(yīng)部位注射0.2 mL生理鹽水作為對(duì)照，每周注射1次至處死。注射4、8周后兩組各處死6只實(shí)驗(yàn)動(dòng)物，大體觀察跟腱情況后，取雙側(cè)跟腱HE染色觀察細(xì)胞結(jié)構(gòu)、基質(zhì)形態(tài)，苦味酸-天狼星紅染色偏振光顯微鏡下觀察肌腱組織的膠原變化并定量分析Ⅰ、Ⅲ型膠原含量，透射電鏡觀測(cè)膠原纖維密度及直徑。 結(jié)果  HE染色示兩組實(shí)驗(yàn)側(cè)均出現(xiàn)膠原纖維結(jié)構(gòu)破壞?？辔端?天狼星紅染色示4、8周時(shí)兩組實(shí)驗(yàn)側(cè)Ⅲ型膠原纖維均較對(duì)照側(cè)增加，Ⅰ型膠原減少（P  lt; 0.05）；與低劑量組比較，高劑量組實(shí)驗(yàn)側(cè)Ⅲ型膠原纖維增加，Ⅰ型膠原減少，Ⅲ/Ⅰ型膠原比值增高（P  lt; 0.05）。透射電鏡示兩組4、8周時(shí)實(shí)驗(yàn)側(cè)單位面積內(nèi)總膠原纖維橫截面積所占百分比均較對(duì)照側(cè)降低，直徑 gt; 100 nm的纖維比例均較對(duì)照側(cè)降低，直徑 lt; 100 nm的纖維比例均增加（P  lt; 0.05）；與低劑量組比較，高劑量組實(shí)驗(yàn)側(cè)單位面積內(nèi)總膠原纖維橫截面積所占百分比更低，直徑 gt; 100 nm的纖維比例均明顯降低，直徑 lt; 100 nm的比例明顯增加（P  lt; 0.05）。 結(jié)論  重復(fù)注射PGE2能導(dǎo)致兔跟腱Ⅰ型膠原減少，Ⅲ型膠原增多，Ⅰ/Ⅲ型膠原比例倒置，單位面積總膠原纖維密度降低，直徑變細(xì)，可能與肌腱病發(fā)生相關(guān)。

引用本文： 李輝,唐康來(lái),鄧銀栓,謝美明,常德海,陶旭,許建中. 外源性前列腺素E2對(duì)兔跟腱膠原含量的影響. 中國(guó)修復(fù)重建外科雜志, 2012, 26(3): 352-358. doi: 復(fù)制

1. Walz DM, Newman JS, Konin GP, et al. Epicondylitis: pathogenesis, imaging, and treatment. Radiographics, 2010, 30(1): 167-184.
2. Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports, 2008, 18(1): 3-15.
3. Fu SC, Rolf C, Cheuk YC, et al. Deciphering the pathogenesis of tendinopathy: a three-stages process. Sports Med Arthrosc Rehabil Ther Technol, 2010, 2: 30.
4. Li Z, Yang G, Khan M, et al. Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching. Am J Sports Med, 2004, 32(2): 435-440.
5. Bosetti F, Langenbach R, Weerasinghe GR. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. J Neurochem, 2004, 91(6): 1389-1397.
6. Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol, 2006, 119(3): 229-240.
7. Yucel-Lindberg T, Olsson T, Kawakami T. Signal pathways involved in the regulation of prostaglandin E synthase-1 in human gingival fibroblasts. Cell Signal, 2006, 18(12): 2131-2142.
8. Langberg H, Skovgaard D, Karamouzis M, et al. Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. J Physiol, 1999, 515(Pt3): 919-927.
9. Kjaer M, Langberg H, Heinemeier K, et al. From mechanical loading to collagen synthesis, structural changes and function in human tendon. Scand J Med Sci Sports, 2009, 19(4): 500-510.
10. Yao L, Bestwick CS, Bestwick LA, et al. Phenotypic drift in human tenocyte culture. Tissue Eng, 2006, 12(7): 1843-1849.
11. Khan MH, Li Z, Wang JH. Repeated Exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration. Clin J Sport Med, 2005, 15(1): 27-33.
12. Wang JH. Mechanobiology of tendon. J Biomech, 2006, 39(9): 1563-1582.
13. Oliva F, Via AG, Maffulli N. Calcific tendinopathy of the rotator cuff tendones. Sports Med Arthrosc, 2011, 19(3): 237-243.
14. Arnoczky SP, Lavagnino M, Egerbacher M, et al. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med, 2007, 35(5): 763-769.
15. 曹洪輝, 唐康來(lái), 陳磊, 等. 新型肌腱細(xì)胞循環(huán)牽伸載荷系統(tǒng)的研制及運(yùn)行效果觀察. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2010, 32(6): 507-510.
16. 鄧銀栓, 唐康來(lái), 謝美明, 等. 不同牽伸載荷對(duì)體外培養(yǎng)人肌腱細(xì)胞纖維型肌動(dòng)蛋白的影響. 中華醫(yī)學(xué)雜志, 2011, 91(25): 1780-1785.
17. 謝美明, 唐康來(lái), 鄧銀栓, 等. 不同牽伸強(qiáng)度對(duì)體外人肌腱細(xì)胞磷脂酶A2/環(huán)氧合酶表達(dá)的影響. 中華創(chuàng)傷雜志, 2011, 27(9): 822-826.
18. Lui PP, Chan LS, Lee YW, et al. Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford), 2010, 49(2): 231-239.
19. Riley G. Tendinopathy—from basic science to treatment. Nat Clin Pract Rheumatol, 2008, 4(2): 82-89.
20. O’Keeffe SA, Hogan BA, Eustace SJ, et al. Overuse injuries of the knee. Magn Reson Imaging Clin N Am, 2009, 17(4): 725-739.
21. Pearce CJ, Ismail M, Calder JD. Is apoptosis the cause of noninsertional achilles tendinopathy? Am J Sports Med, 2009, 37(12): 2440-2444.
  1. 1. Walz DM, Newman JS, Konin GP, et al. Epicondylitis: pathogenesis, imaging, and treatment. Radiographics, 2010, 30(1): 167-184.
  2. 2. Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports, 2008, 18(1): 3-15.
  3. 3. Fu SC, Rolf C, Cheuk YC, et al. Deciphering the pathogenesis of tendinopathy: a three-stages process. Sports Med Arthrosc Rehabil Ther Technol, 2010, 2: 30.
  4. 4. Li Z, Yang G, Khan M, et al. Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching. Am J Sports Med, 2004, 32(2): 435-440.
  5. 5. Bosetti F, Langenbach R, Weerasinghe GR. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. J Neurochem, 2004, 91(6): 1389-1397.
  6. 6. Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol, 2006, 119(3): 229-240.
  7. 7. Yucel-Lindberg T, Olsson T, Kawakami T. Signal pathways involved in the regulation of prostaglandin E synthase-1 in human gingival fibroblasts. Cell Signal, 2006, 18(12): 2131-2142.
  8. 8. Langberg H, Skovgaard D, Karamouzis M, et al. Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. J Physiol, 1999, 515(Pt3): 919-927.
  9. 9. Kjaer M, Langberg H, Heinemeier K, et al. From mechanical loading to collagen synthesis, structural changes and function in human tendon. Scand J Med Sci Sports, 2009, 19(4): 500-510.
  10. 10. Yao L, Bestwick CS, Bestwick LA, et al. Phenotypic drift in human tenocyte culture. Tissue Eng, 2006, 12(7): 1843-1849.
  11. 11. Khan MH, Li Z, Wang JH. Repeated Exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration. Clin J Sport Med, 2005, 15(1): 27-33.
  12. 12. Wang JH. Mechanobiology of tendon. J Biomech, 2006, 39(9): 1563-1582.
  13. 13. Oliva F, Via AG, Maffulli N. Calcific tendinopathy of the rotator cuff tendones. Sports Med Arthrosc, 2011, 19(3): 237-243.
  14. 14. Arnoczky SP, Lavagnino M, Egerbacher M, et al. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med, 2007, 35(5): 763-769.
  15. 15. 曹洪輝, 唐康來(lái), 陳磊, 等. 新型肌腱細(xì)胞循環(huán)牽伸載荷系統(tǒng)的研制及運(yùn)行效果觀察. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2010, 32(6): 507-510.
  16. 16. 鄧銀栓, 唐康來(lái), 謝美明, 等. 不同牽伸載荷對(duì)體外培養(yǎng)人肌腱細(xì)胞纖維型肌動(dòng)蛋白的影響. 中華醫(yī)學(xué)雜志, 2011, 91(25): 1780-1785.
  17. 17. 謝美明, 唐康來(lái), 鄧銀栓, 等. 不同牽伸強(qiáng)度對(duì)體外人肌腱細(xì)胞磷脂酶A2/環(huán)氧合酶表達(dá)的影響. 中華創(chuàng)傷雜志, 2011, 27(9): 822-826.
  18. 18. Lui PP, Chan LS, Lee YW, et al. Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford), 2010, 49(2): 231-239.
  19. 19. Riley G. Tendinopathy—from basic science to treatment. Nat Clin Pract Rheumatol, 2008, 4(2): 82-89.
  20. 20. O’Keeffe SA, Hogan BA, Eustace SJ, et al. Overuse injuries of the knee. Magn Reson Imaging Clin N Am, 2009, 17(4): 725-739.
  21. 21. Pearce CJ, Ismail M, Calder JD. Is apoptosis the cause of noninsertional achilles tendinopathy? Am J Sports Med, 2009, 37(12): 2440-2444.