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双氯芬酸钠对啮齿动物模型中骨形态发生蛋白诱导的炎症的影响。

Effects of Diclofenac Sodium on BMP-induced Inflammation in a Rodent Model.

作者信息

Ye Shuai, Yim Jong-Han, Kim Jung-Ryul, Jang Kyu Yun, Wang Hongen, Wang Jeffrey C, Lee Kwang-Bok

机构信息

*Departments of Orthopaedic Surgery †Pathology ‡Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea; and §Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA.

出版信息

Spine (Phila Pa 1976). 2015 Jul 15;40(14):E799-807. doi: 10.1097/BRS.0000000000000926.

DOI:10.1097/BRS.0000000000000926
PMID:26164161
Abstract

STUDY DESIGN

Prospective in vivo rodent model of bone morphogenetic protein (BMP)-induced inflammation.

OBJECTIVE

To evaluate the effects of the coadministration of the nonsteroidal anti-inflammatory drug, diclofenac, on BMP-induced inflammation using our rodent model.

SUMMARY OF BACKGROUND DATA

The use of BMP-2 is associated with inflammation in the neck and back. We have previously reported on a rodent model of BMP-2-induced inflammation.

METHODS

Seven treatment groups were: Surgery alone; absorbable collagen sponges (ACS) alone; 20 μg rhBMP-2 on ACS with no diclofenac; 20 μg rhBMP-2 on ACS+50 mg diclofenac injections; 20 μg rhBMP-2 on ACS+75 mg diclofenac; 20 μg rhBMP-2 on ACS+100 mg diclofenac; and 20 μg rhBMP-2 on ACS+125 mg diclofenac. Using magnetic resonance imaging, inflammation (soft tissue edema volume) was assessed at 3 hours and at 2, 7, and 14 days after implantation. Western blot analysis, histology, and immunohistochemical staining were performed to compare the inflammatory response between groups. The mass size and tissue density of bone formation were compared between groups using plain radiography.

RESULTS

Soft-tissue edema volumes in all diclofenac-treated groups were significantly lower than those observed in the rhBMP-2 alone. There was no significant difference in soft tissue edema volumes between 4 diclofenac-treated groups. The expression of NF-κB signaling pathway related proteins (p65 and p-p65) were increased in the rhBMP-2+ACS group and decreased in diclofenac treatment groups. Histological findings and immunohistochemical staining were consistent with the Western blot results. There was no significant difference between the rhBMP-2+ACS group and diclofenac treatment groups in terms of the mass size and tissue density of bone formation.

CONCLUSION

Coadministration of diclofenac sodium can reduce the inflammatory response to BMP-2 without impairing heterotopic bone formation in our rodent model of BMP-2-induced inflammation.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

骨形态发生蛋白(BMP)诱导炎症的前瞻性体内啮齿动物模型。

目的

使用我们的啮齿动物模型评估非甾体抗炎药双氯芬酸联合给药对BMP诱导炎症的影响。

背景数据总结

BMP-2的使用与颈部和背部炎症相关。我们之前报道过BMP-2诱导炎症的啮齿动物模型。

方法

七个治疗组分别为:单纯手术;单纯可吸收胶原海绵(ACS);ACS上使用20μg重组人骨形态发生蛋白-2(rhBMP-2)且不使用双氯芬酸;ACS上使用20μg rhBMP-2 + 50mg双氯芬酸注射;ACS上使用20μg rhBMP-2 + 75mg双氯芬酸;ACS上使用20μg rhBMP-2 + 100mg双氯芬酸;以及ACS上使用20μg rhBMP-2 + 125mg双氯芬酸。使用磁共振成像,在植入后3小时以及2、7和14天评估炎症(软组织水肿体积)。进行蛋白质印迹分析、组织学检查和免疫组织化学染色以比较各组之间的炎症反应。使用X线平片比较各组之间骨形成的肿块大小和组织密度。

结果

所有双氯芬酸治疗组的软组织水肿体积均显著低于单独使用rhBMP-2组观察到的体积。4个双氯芬酸治疗组之间的软组织水肿体积无显著差异。rhBMP-2 + ACS组中NF-κB信号通路相关蛋白(p65和p-p65)的表达增加,而在双氯芬酸治疗组中降低。组织学结果和免疫组织化学染色与蛋白质印迹结果一致。rhBMP-2 + ACS组与双氯芬酸治疗组在骨形成的肿块大小和组织密度方面无显著差异。

结论

在我们的BMP-2诱导炎症的啮齿动物模型中,双氯芬酸钠联合给药可降低对BMP-2的炎症反应,而不损害异位骨形成。

证据水平

无。

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