Xiong Chengjie, Daubs Michael D, Montgomery Scott R, Aghdasi Bayan, Inoue Hirokazu, Tian Haijun, Suzuki Akinobu, Tan Yanlin, Hayashi Tetsuo, Ruangchainikom Monchai, Chai Timothy, Corey Megan, Wang Jeffrey C
*Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China †Department of Orthopaedic Surgery, University of California at Los Angeles (UCLA), Los Angeles, CA; and ‡Orthopaedic Spine Department, Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Spine (Phila Pa 1976). 2013 Sep 1;38(19):1640-7. doi: 10.1097/BRS.0b013e31829cf348.
Basic science rodent model of bone morphogenetic protein-2 (BMP-2) soft-tissue inflammation.
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.
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.
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.
Magnetic resonance imaging volume rendering demonstrated inflammatory edema decreased by 49% from 605.4 mm to 304.03 mm 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 mm to 1.31 mm 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).
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.
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。
本研究调查了人等效剂量(HDE)地塞米松(DM)对啮齿动物模型中BMP-2相关软组织炎症的抗炎作用,并提出脊柱外科临床实践中合适的使用剂量。
BMP-2常用于脊柱手术以增强融合。然而,已观察到软组织炎症的副作用。DM可减少促炎细胞因子的产生和细胞免疫反应。然而,HDE DM在BMP-2相关软组织炎症啮齿动物模型中的抗炎作用尚未见报道。
对接受BMP-2椎旁植入物的啮齿动物队列在围手术期给予5、10和15mg的HDE DM,给药3次,并与仅使用BMP-2的阳性对照和磷酸盐缓冲液阴性对照进行比较(每组n = 6只动物)。组织病理学、磁共振成像和大体解剖被用作细胞、水肿和渗出性炎症反应的测量指标。在术后第2天和第7天进行系列处死。
磁共振成像容积再现显示,接受5、10或15mg HDE DM治疗的动物炎症水肿从605.4mm³降至304.03mm³,减少了49%(P < 0.05)。组织病理学分析显示,接受5、10或15mg HDE DM治疗的动物炎症横截面积从1.84mm²降至1.31mm²,减少了28.8%(P < 0.05)。接受15mg HDE DM治疗的动物免疫细胞浸润深度从0.26mm降至0.16mm,减少了38.5%(P < 0.05)。接受10或15mg HDE DM治疗的动物中,100%预防了大体解剖学上的炎症渗出(P < 0.05)。
低剂量DM给药可有效控制BMP-2引起的细胞炎症和水肿。脊柱外科医生可考虑使用10或15mg DM来控制BMP-2脊柱手术中出现的炎症和水肿。