BMP-2 Adverse Reactions Treated With Human Dose Equivalent Dexamethasone in a Rodent Model of Soft-Tissue Inflammation
BMP-2 Adverse Reactions Treated With Human Dose Equivalent Dexamethasone in a Rodent Model of Soft-Tissue Inflammation
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DOI：
10.1097/brs.0b013e31829cf348
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发表时间：
2013-09
期刊：
影响因子：
3
通讯作者：
C. Xiong;M. Daubs;S. Montgomery;B. Aghdasi;H. Inoue;Haijun Tian;A. Suzuki;Yanlin Tan;Tetsuo Hayashi;Monchai Ruangchainikom;Timothy Chai;M. Corey;Jeffrey C. Wang
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作者：
C. Xiong;M. Daubs;S. Montgomery;B. Aghdasi;H. Inoue;Haijun Tian;A. Suzuki;Yanlin Tan;Tetsuo Hayashi;Monchai Ruangchainikom;Timothy Chai;M. Corey;Jeffrey C. Wang
研究设计。骨形态发生蛋白-2 （BMP-2）软组织炎症的基础科学啮齿动物模型。目标。本研究在啮齿动物模型中研究了人剂量当量（HDE）地塞米松（DM）治疗bmp -2相关软组织炎症的抗炎作用，并建议在脊柱外科医生的临床实践中使用合适的剂量。背景资料摘要。BMP-2常用于脊柱手术以增强融合。然而，软组织炎症的副作用已经被观察到。糖尿病降低促炎细胞因子的产生和细胞免疫反应。然而，HDE DM在bmp -2相关软组织炎症的啮齿动物模型中的抗炎作用尚未报道。方法。对接受BMP-2椎旁植入物的啮齿动物队列围手术期给予5、10和15 mg HDE DM 3次，并与BMP-2阳性对照组和磷酸盐缓冲液阴性对照组进行比较（每组n = 6例）。组织病理学、磁共振成像和大体解剖被用来衡量细胞、水肿和渗出性炎症反应。分别于术后第2天和第7天进行连环杀人。结果。磁共振成像显示，在接受5、10或15 mg HDE DM治疗的受试者中，炎症性水肿从605.4 mm3减少到304.03 mm3，减少了49% （P < 0.05）。组织病理学分析显示，接受5、10或15 mg HDE DM治疗的受试者炎症横截面积从1.84 mm2减少到1.31 mm2，减少了28.8% （P < 0.05）。15 mg HDE DM组免疫细胞浸润深度由0.26 mm下降至0.16 mm，降低38.5% （P < 0.05）。使用10或15 mg HDE DM治疗的受试者中，100%的人都能防止大体解剖性炎症渗出（P < 0.05）。结论。低剂量DM可有效控制BMP-2引起的细胞炎症和水肿。脊柱外科医生可能会考虑10或15mg DM来控制BMP-2脊柱手术中出现的炎症和水肿。
Study Design. Basic science rodent model of bone morphogenetic protein-2 (BMP-2) soft-tissue inflammation. Objective. This study investigated the anti-inflammatory effect of human dose equivalent (HDE) dexamethasone (DM) for treatment of BMP-2-related soft-tissue inflammation in a rodent model and suggests an appropriate dose for utilization in the clinical practice of spine surgeons. Summary of Background Data. BMP-2 is frequently used in spinal surgery to augment fusion. Yet, side effects of soft-tissue inflammation have been observed. DM decreases proinflammatory cytokine production and cellular immune response. However, the anti-inflammatory effects of HDE DM in a rodent model of BMP-2-associated soft-tissue inflammation have not been reported. Methods. Five, 10, and 15 mg of HDE DM were administered 3 times perioperatively to rodent cohorts receiving BMP-2 paraspinal implants and compared against BMP-2 only positive controls and phosphate buffer negative controls (n = 6 subjects per group). Histopathology, magnetic resonance imaging, and gross dissection were used as measures of cellular, edematous, and exudative inflammatory response. Serial killings were made on day 2 and day 7 postoperatively. Results. Magnetic resonance imaging volume rendering demonstrated inflammatory edema decreased by 49% from 605.4 mm3 to 304.03 mm3 in subjects treated with 5, 10, or 15 mg of HDE DM (P < 0.05). Histopathological analysis demonstrated inflammatory cross-sectional area decreased 28.8% from 1.84 mm2 to 1.31 mm2 in subjects treated with 5, 10 or 15 mg of HDE DM (P < 0.05). Immune cellular infiltration depth decreased 38.5% from 0.26 mm to 0.16 in subjects treated with 15 mg of HDE DM (P < 0.05). Gross anatomical inflammatory exudates were prevented in 100% of subjects treated with 10 or 15 mg of HDE DM (P < 0.05). Conclusion. Low-dose DM administration is effective in controlling the cellular inflammation and edema resulting from BMP-2. Ten or 15 mg of DM might be considered by spine surgeons for controlling the inflammation and edema seen in spine surgery with BMP-2.