人胰岛素样生长因子-1在急性损伤肩袖腱-骨愈合过程中的组织学研究

Histologic analysis of the effect of tendon-to-bone healing by transforming insulin-like growth factor-1(IGF-1) in rotator cuff repair

目的应用大鼠建立急性肩袖损伤模型,观察人胰岛素样生长因子-1(rhIGF-1)在腱-骨愈合过程中的作用。方法取16只成年雄性SD大鼠,均行右侧冈上肌切断术,建立急性肩袖损伤模型。随机分为2组:空白组(生理盐水)、实验组(rhIGF-1/IGFBP-3 4.0mg/kg/day),术后第1天开始,连续14天于腹部皮下注射。术后1周和4周,各组取4只大鼠以冈上肌腱的重建止点为中心取材。经苏木精-伊红染色和免疫组化定位增殖细胞核抗原(proliferating cell nuclear antigen、 PCNA)和Ⅷ因子(FactorⅧ)定性评估细胞增殖和新生血管形成;应用苦味酸天狼猩红染色,采用偏光显微镜半定量分析在腱-骨插入位点的胶原纤维组织的连续性和排列规律性。结果术后1周时,苏木精-伊红染色光学显微镜下观察,实验组较对照组在腱-骨插入位点和肌腱腱实质部均显示较多细胞增殖和血管生成。实验组较对照组增殖细胞核抗原免疫组化提示有更积极的细胞分裂,内皮细胞Ⅷ因子免疫组化提示局部有更丰富内皮细胞;术后4周苏木精-伊红染色,实验组局部出现了不成熟的类软骨细胞。苦味酸天狼猩红染色,实验组较对照组更可见排列规则的兰染的软骨基质,且和骨质连接紧密,其间可见少量纤维软骨细胞,骨质和纤维软骨带界限更清晰。结论人胰岛素样生长因子-1能促使细胞增殖,形成类似于肩袖天然纤维软骨插入点,为临床促进腱骨愈合提供了一种思路。

Objective To investigate the roles of insulin-like growth factor-1(IGF-1)in tendon-to-bone healing after supraspinatus tendon repair in rats.Methods Sixteen adult male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon.Rats were randomized into one of tow groups:control(repair only),and injected IGF-1(4.0 mg/kg/day)from the first day after surgery.Animals were euthanized 7 days after surgery to assess cellular proliferation and angiogenesis.The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization,fibrocartilage formation and collagen fiber organization with safranin-O staining and hematoxylin-eosin staining.Results The repaired supraspinatus tendon was in continuity with the bone in all animals.At7 days,IGF-1 demonstrated a positive response in cellular proliferation and angiogenesis compared with the control.At4 weeks,IGF-1 had effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls.Conclusion IGF-1 in vivo injection can significantly promote the healing of tendon-to-bone after supraspinatus tendon repair in rats.