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Influence of glucocorticoid and bone morphogenetic protein on fracture healing using a rat closed femoral fracture model.

機(jī)譯：糖皮質(zhì)激素和骨形態(tài)發(fā)生蛋白對(duì)大鼠閉合股骨骨折模型骨折愈合的影響。

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摘要

The purpose of this study was to examine the effects of pharmocologic doses of prednisolone on fracture healing using a closed femoral fracture model in the rat and to determine whether the bone morphogenetic protein, osteogenic protein-1 (OP-1), would augment fracture healing during glucocorticoid therapy. One hundred and ninety-two male Sprague-Dawley rats received subcutaneous implants of either timed-release prednisolone (equivalent to 2.2 mg/kg/day) or placebo pellets. Two weeks following implantation, surgery was performed for intramedullary pin placement and subsequent femur fracture using the established closed fracture method in the rat. In a subset of rats, a limited approach to the femur was performed for application of OP-1 and collagen carrier or collagen carrier alone. Femurs were harvested at 10, 28, and 42 days for radiographic analysis, at 28 and 42 days for biomechanic analysis, and at 3, 10, 21, 28, and 42 days for histomorphometric analysis. For the groups used to evaluate the effects of prednisolone, radiographs showed no significant difference in fracture callus at 10 days. However, measurements at 28, and 42 days revealed significantly less fracture callus in rats treated with prednisolone. Femurs harvested at 28 days for biomechanic analysis withstood significantly less maximum torsion to failure and were significantly reduced in stiffness in rats treated with prednisolone. Histomorphometric analysis revealed significantly less total callus at 21, and 42 days, and less hard callus at 42 days in prednisolone treated rats. However, cartilaginous soft callus was greater in rats treated with prednisolone at 42 days. Differences between prednisolone treatment and control groups for application of OP-1 or collagen alone were not detected for radiographic, biomechanic, or histomorphometric analyses at any time. However, comparison of application of OP-1 or collagen alone in prednisolone treatment groups revealed significantly greater fracture healing with OP-1 compared to collagen alone. These results show that prednisolone treatment significantly inhibits fracture healing, and specifically inhibits the process of endochondral ossification. OP-1 is highly effective in counteracting the inhibitory effects of prednisolone treatment on fracture healing, and may be an important adjunct to fracture repair in patients receiving glucocorticoid therapy.
機(jī)譯：這項(xiàng)研究的目的是使用大鼠股骨閉合性骨折模型檢查藥物劑量的潑尼松龍對(duì)骨折愈合的影響，并確定骨形態(tài)發(fā)生蛋白骨生成蛋白1（OP-1）是否會(huì)促進(jìn)骨折愈合在糖皮質(zhì)激素治療期間。一百九十二只雄性Sprague-Dawley大鼠接受了定時(shí)釋放的潑尼松龍（相當(dāng)于2.2 mg / kg /天）或安慰劑顆粒的皮下植入。植入后兩周，使用已建立的閉合骨折方法在大鼠中進(jìn)行了髓內(nèi)釘放置和隨后的股骨骨折的手術(shù)。在一部分大鼠中，僅使用OP-1和膠原蛋白載體或膠原蛋白載體對(duì)股骨進(jìn)行了有限的處理。在第10、28和42天收獲股骨用于放射線照相分析，在28和42天進(jìn)行生物力學(xué)分析，并在3、10、21、28和42天進(jìn)行組織形態(tài)分析。對(duì)于用于評(píng)估潑尼松龍效果的組，X光片顯示在10天時(shí)骨折call沒有顯著差異。但是，在第28天和第42天進(jìn)行的測(cè)量顯示，潑尼松龍治療的大鼠的骨折call明顯減少。在28天時(shí)收獲的股骨用于生物力學(xué)分析，其最大的扭轉(zhuǎn)失敗率顯著降低，并且在潑尼松龍治療的大鼠中，其剛度明顯降低。組織形態(tài)計(jì)量學(xué)分析顯示在潑尼松龍治療的大鼠中，第21天和第42天的總愈傷組織明顯減少，而第42天的硬性愈傷組織更少。然而，在第42天用潑尼松龍治療的大鼠中，軟骨軟call愈大。在任何時(shí)候，射線照相，生物力學(xué)或組織形態(tài)計(jì)量學(xué)分析均未檢測(cè)到潑尼松龍治療組和對(duì)照組僅應(yīng)用OP-1或膠原蛋白之間的差異。但是，在潑尼松龍治療組中單獨(dú)應(yīng)用OP-1或膠原蛋白的比較顯示，與單獨(dú)使用膠原蛋白相比，OP-1的骨折愈合顯著增強(qiáng)。這些結(jié)果表明潑尼松龍治療顯著抑制骨折愈合，特別是抑制軟骨內(nèi)骨化的過(guò)程。 OP-1在抵消潑尼松龍治療對(duì)骨折愈合的抑制作用方面非常有效，并且可能是接受糖皮質(zhì)激素治療的患者骨折修復(fù)的重要輔助手段。

著錄項(xiàng)

  • 作者

    Gilley, Robert Stuart.;

  • 作者單位

    University of Minnesota.;

  • 授予單位 University of Minnesota.;
  • 學(xué)科 Biology Veterinary Science.
  • 學(xué)位 Ph.D.
  • 年度 2002
  • 頁(yè)碼 130 p.
  • 總頁(yè)數(shù) 130
  • 原文格式 PDF
  • 正文語(yǔ)種 eng
  • 中圖分類 動(dòng)物學(xué);
  • 關(guān)鍵詞

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