辛伐他汀促进兔肩袖损伤修复术后腱-骨愈合的实验研究

Experimental Study on Simvastatin/Methylcellulose Gel Promoting Tendon-bone Healing after Acute Rotator Cuff Repair in Rabbits

目的:探讨辛伐他汀/甲基纤维素凝胶对兔肩袖损伤修复术后腱-骨愈合的影响。方法:将36只成年雄性新西兰大白兔随机分为实验组、实验对照组、空白对照组,每组各12只。建立兔肩袖损伤修复模型后,实验组在肱骨大结节骨槽上注射辛伐他汀/甲基纤维素凝胶并将冈上肌缝合回足印区;实验对照组仅注射甲基纤维素凝胶并缝合回足印区;空白对照组不给予任何干预措施缝合回足印区。术后连续3天肌注庆大霉素(3mg/kg),无须制动固定。所有兔子在术后2、4、8周处死,取冈上肌与近端肱骨的交界区行甲苯胺蓝染色、血管内皮生长因子(VEGF)免疫组化染色、Masson染色及生物力学检测。观察兔冈上肌腱-骨愈合情况。结果:(1)生物力学结果显示:三组术后腱-骨界面的最大载荷及刚度随着时间点的延长而不断增强,差异有统计学意义(P<0.05);术后2周,实验组腱-骨界面的最大载荷及刚度与实验对照组及空白对照组比较无差异(P>0.05);术后4周及8周,实验组腱-骨界面的最大载荷及刚度显著高于实验对照组及空白对照组(P<0.05)。(2)甲苯胺蓝染色结果显示:术后2周,实验组腱-骨界面的成纤维细胞较对照组多;4周及8周见较多新生软骨细胞及骨细胞且腱-骨结合较对照组致密。(3)免疫组化结果显示:术后2周,实验组VEGF阳性细胞表达明显高于实验对照组及空白对照组(P<0.05);术后4周及8周,三组腱-骨界面的VEGF表达趋于下降。(4)Masson染色结果显示:术后4周,实验组腱-骨界面胶原纤维的走形及生成情况均优于其余两组。结论:局部应用辛伐他汀/甲基纤维素凝胶能够促进兔肩袖损伤术后腱-骨愈合,增强腱骨界面的生物力学强度。

Objective To investigate the effect of the simvastatin/methylcellulose gel promoting tendon-bone healing after the repair of the acute rotator cuff injury of rabbits.MethodsThirty-six adult maleNew Zealand white rabbits were randomly divided into an experimental group,an experimental controlgroup and a blank control group,each of 12. After the rotator cuff repair model was established inthe rabbits,the simvastatin/methylcellulose gel and the methylcellulose gel alone were injected into thebone trough of the large tuberosity of the humerus in the experimental and experimental control groupsrespectively,and the supraspinatus was sutured back to the foot print area,while the blank controlgroup was not given any injection and the supraspinatus was sutured back to the foot print area. Gentamicin(3 mg/kg) was injected for 3 days after the operation without immobilization. All rabbits werekilled 2,4 and 8 weeks after the operation and the junction of the supraspinatus and proximal humerus was subjected to the toluidine blue staining,vascular endothelial growth factor(VEGF) immunohistochemical staining and biomechanical test.ResultsThe biomechanical results revealed that the maximalload and stiffness of the tendon-groups with the prolongation of time. Two weeks after the operation,there were no significant differences between the control groups in the maximal load and stiffness of tendon bone interface,while 4 and8 weeks after the operation,the two values of the experimental group were significantly higher thanthe controls(P>0.05). The toluidine blue staining results showed that 2 weeks after surgery,the fibroblast cells at the tendon bone interface in the experimental group were significantly more than the control groups. More chondrocytes and osteoblasts were seen in the experimental group 4 and 8 weeks after the operation,and the tendon-bone binding was denser than that in the control group. The immunohistochemical results showed that the expression of VEGF positive cells in the experimental groupwas significantly higher than the control groups 2 weeks after the operation(P<0.05),but decreased 4 and 8 weeks after the operation. The results of Masson staining showed that the shape and productionof collagen fibers at the tendon-bone interface in the experimental group were better than the othertwo groups 4 weeks after the operation.ConclusionThe local application of simvastatin/methylcellulosegel can promote the tendon-bone healing and enhance the biomechanical strength of the tendon-boneinterface of rabbits after their rotator cuff injury.