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在软组织炎症的啮齿动物模型中,用人等效剂量地塞米松治疗BMP-2不良反应。

BMP-2 adverse reactions treated with human dose equivalent dexamethasone in a rodent model of soft-tissue inflammation.

作者信息

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

机构信息

*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.

出版信息

Spine (Phila Pa 1976). 2013 Sep 1;38(19):1640-7. doi: 10.1097/BRS.0b013e31829cf348.

DOI:10.1097/BRS.0b013e31829cf348
PMID:23715023
Abstract

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 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).

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.

摘要

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。

目的

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。

背景数据总结

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。

方法

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。

结果

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)。

结论

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。

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