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山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (3): 27-31.doi: 10.6040/j.issn.1671-7554.0.2014.887

• 基础医学 • 上一篇    下一篇

局部应用辛伐他汀促进前交叉韧带重建骨隧道腱骨愈合的效应

林锦秀1, 孙东升1, 郑潇1, 尹德超1, 李晔1, 张磊2   

  1. 1. 淄博市第一医院骨一科, 山东 淄博 255200;
    2. 淄博市第一医院病理科, 山东 淄博 255200
  • 收稿日期:2014-11-28 修回日期:2015-02-08 出版日期:2015-03-10 发布日期:2015-03-10
  • 通讯作者: 林锦秀, E-mail:drlinjx@qq.com E-mail:drlinjx@qq.com

Enhancement of tendon-bone healing by topical use of simvastatin after ACL reconstruction

LIN Jinxiu1, SUN Dongsheng1, ZHENG Xiao1, YIN Dechao1, LI Ye1, ZHANG Lei2   

  1. 1. Department of Orthopedics, First Hospital of Zibo City, Zibo 255200, Shandong, China;
    2. Department of Pathology, First Hospital of Zibo City, Zibo 255200, Shandong, China
  • Received:2014-11-28 Revised:2015-02-08 Online:2015-03-10 Published:2015-03-10

摘要: 目的 探讨局部应用辛伐他汀促进腱骨愈合的效应。方法 采用15只大白兔建立实验模型, 取自体趾长屈肌腱进行前交叉韧带(ACL)重建, 胫骨侧应用螺钉固定, 股骨侧采用悬吊固定。左侧作为实验侧, 在股骨隧道远关节侧填塞入辛伐他汀明胶海绵复合物;右侧为对照侧, 填塞入明胶海绵。术后2、4、8周各处死3只做组织学检查, 术后8周处死6只做生物力学检查, 观察腱骨愈合情况, 通过对比判断辛伐他汀促进腱骨愈合的效应。结果 实验侧术后2周腱骨界面见大量新生血管, 结合紧密;4周可见大量sharpey纤维形成;8周腱骨界面模糊, 可见分层软骨。对照侧术后4周未见sharpey纤维形成, 8周见sharpey纤维形成。生物力学检测发现, 术后8周实验侧股骨隧道拉脱负荷高于对照侧, 差异有统计学意义(P<0.05)。结论 局部应用辛伐他汀具有促进ACL重建骨隧道腱骨愈合的作用。

关键词: 腱骨愈合, 前交叉韧带, 重建, 辛伐他汀

Abstract: Objective To evaluate the enhancement potential of topical use of simvastatin for tendon-bone healing. Methods A total of 15 rabbits were enrolled to establish anterior cruciate ligament (ACL) reconstruction models. The tibial side was screw fixed while the femoral side was suspending fixed in both knees of the rabbits. Simvastatin was inserted into the left knee (experimental side) bone tunnel with a gelatin sponge carrier, while gelatin sponge was inserted into the right knee (control side) bone tunnel. Three rabbits were sacrificed in week 2, 4 and 8 postoperatively. Tendon-bone interface was histologically assessed. Six rabbits were sacrificed for biomechanical tests in week 8. Results Histological analysis in week 2 demonstrated that tendon-bone healing was significantly greater with angiogenesis in the simvastatin-treated side than in the control side. In week 4, a great quantity of sharpey fibers at tendon-bone interface were observed in the experimental side, yet there were no sharpey fibers in the control side. In week 8, tendon-bone interface was narrow and unclear in the experimental side, yet a few sharpey fibers were observed in the control side. The average load to failure in the experimental side was significantly greater than in the control side. Conclusion Topical use of simvastatin promotes the tendon-bone healing after ACL reconstruction.

Key words: Reconstruction, Simvastatin, Tendon-bone healing, Anterior cruciate ligament

中图分类号: 

  • R686.5
[1] Park JB. The use of simvastatin in bone regeneration[J]. Med Oral Patol Oral Cir Bucal, 2009,14(9):485-488.
[2] Montero J, Manzano G, Albaladejo A. The role of topical simvastatin on bone regeneration:A systematic review[J]. J Clin Exp Dent, 2014, 6(3):286-290.
[3] Chen CH. Graft healing in anterior cruciate ligament reconstruction[J]. Sports Med Arthrosc Rehabil Ther Technol, 2009, 1(1):21.
[4] 王永健, 敖英芳. 自体半腱肌腱重建兔前交叉韧带腱骨愈合和止点形成实验研究[J]. 中国运动医学杂志, 2007, 26(1):5-9. WANG Yongjian, AO Yingfang. Experimental study on tendon-bone healing and insertion formation in anterior cruciate ligament reconstruction using semitendinosus tendon autograft in a rabbit moldel[J].Sports Med, 2007, 26(1):5-9.
[5] 邝冠明, 邱伟鹏, 吕维加, 等. 促进前交叉韧带重建术后腱-骨愈合的方法学进展[J]. 中国骨与关节外科, 2010, 3(3):235-244.
[6] 周玉坤, 彭鸿灵. 不同材料重建前交叉韧带腱骨愈合的系统评价[J]. 中国组织工程研究与临床康复, 2010, 14(25):4737-4740. ZHOU Yukun, PENG Hongling. Evaluation on different materials for anterior cruciate ligament reconstruction and tendon bone healing[J]. Journal of Clinical Rehabilitative Tissue Engineering Research, 2010, 14(25):4737-4740.
[7] Yamashita M, Otsuka F, Mukai T, et al. Simvastain antagonizes tumor necrosis factor-alpha inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway[J]. J Endocrinol, 2008, 196(3):601-613.
[8] Tai IC, Fu YC, Wang CK, et al. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair[J]. Int J Nanomedicine, 2013, 8(1):3895-3904.
[9] Tang QO, Tran GT, Gamie Z, et al. Stains:Under investigation for increasing bone mineral density and augmenting fracture healing[J]. Expert Opin Investig Drugs, 2008, 17(10):1435-1463.
[10] Yoshikawa T, Tohyama H, Enomoto H, et al. Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anteriorcruciate ligament reconstruction[J]. Knee Surg Sports Traumatol Arthrosc, 2006, 14(9):804-810.
[11] Maeda T, Kawane T, Horiuchi N. Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation[J]. Endocrinology, 2003, 144(2):681-692.
[12] Glass GE, Jain A. Cochrane corner:bone morphogenetic protein (BMP) for fracture healing in adults[J]. J Hand Surg Eur Vol, 2013 , 38(4):447-449.
[13] Kim JG, Kim HJ, Kim SE, et al. Enhancement of tendon-bone healing with the use of bone morphogenetic protein-2 inserted into the suture anchor hole in a rabbit patellar tendon model[J]. Cytotherapy, 2014, 16(6):857-867.
[14] Rodeo SA, Suzuki K, Deng XH, et al. Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel[J]. Am J sports Med, 1999, 27(4):476-488.
[15] Mundy G, Garrett R, Harris S, et al. Stimulation of bone formation in vitro and in rodents by statins[J]. Science, 1999, 286(5446):1946-1949.
[16] Ibrahim N, Mohamed N, Shuid AN. Update on statins:hope for osteoporotic fracture healing treatment[J]. Curr Drug Targets, 2013, 14(13):1524-1532.
[17] Yoshikawa T, Tohyama H, Katsura T, et al. Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep[J]. Am J Sports Med, 2006, 34(12):1918-1925.
[18] Reinoso RF, Sánchez Navarro A, García MJ, et al. Preclinical pharmacokinetics of statins[J]. Methods Find Exp Clin Pharmacol, 2002, 24(9):593-613.
[19] Thylin MR, McConnell JC, Schmid MJ, et al. Effects of simvastatin gels on murine calvarial bone[J]. J Periodontol. 2002, 73(10):1141-1148
[20] Stein D, Lee Y, Schmid MJ, et al. Local simvastatin effects on mandibular bone growth and inflammation[J]. J Periodontol, 2005, 76(11):1861-1870.
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