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NFκB 必需调节因子结合域肽对骨感染的预防作用:兔模型的实验研究

Prophylactic Effects of NFκB Essential Modulator-Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model.

作者信息

Wu Wen-Jiao, Xia Chang-Liang, Ou Shuan-Ji, Yang Yang, Zhou Xiao-Zhong, Ma Yun-Fei, Hou Yi-Long, Wang Fa-Zheng, Yang Qing-Po, Qi Yong, Xu Chang-Peng

机构信息

Department of Orthopaedics, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People's Republic of China.

Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

出版信息

J Inflamm Res. 2022 Apr 28;15:2745-2759. doi: 10.2147/JIR.S346627. eCollection 2022.

Abstract

INTRODUCTION

Osteomyelitis is characterized by intensive inflammatory bone disease and remains a clinical challenge in orthopedic surgery, despite the advances made in medical and surgical therapies. is a major causative agent of osteomyelitis, causing the progressive inflammatory destruction of bone. Prophylaxis of osteomyelitis during orthopedic surgery is necessary. NFκB essential modulator-binding domain (NBD) peptides are cell-permeable peptide inhibitors of the IκB-kinase complex. The prophylactic effect of NBD peptides in relieving inflammation and inhibiting bone defects in osteomyelitis is still under investigation. Our purpose was to determine the preventive effect of NBD peptides in infection-induced bone defects in osteomyelitis.

METHODS

An osteomyelitis rabbit model was used in this study. The rabbits were divided into four groups: NBD, cefazolin, control, and PBS. Clinical and laboratory indicators of erythrocyte-sedimentation rate, CRP, and TNFα levels were assessed to monitor systemic reactions. The efficacy of NBD peptides in -induced osteomyelitis was evaluated by radiological, histological, and microbiological examinations, immunohistochemistry, immunofluorescence, and micro-CT scans.

RESULTS

In general, NBD peptides effectively reduced clinical signs in rabbits when compared with the control group. Radiography indicated that there was more severe osteomyelitis in the bacterium-infection control group. There was no significance between cefazolin- and NBD-group average scores. The histological results of the lesion slices further confirmed different severity among the groups. Additionally, significant pathological differences were found between the cefazolin and NBD groups, and the PBS group showed no obvious pathological changes.

CONCLUSION

Prophylactic administration of NBD peptides to bone-defect areas inhibited bacterial spread and promoted bone regeneration, making NBD peptides a possible treatment option for prophylaxis in bone infections.

摘要

引言

骨髓炎的特征是严重的炎症性骨病,尽管在药物和手术治疗方面取得了进展,但仍是骨科手术中的一项临床挑战。是骨髓炎的主要病原体,可导致骨的进行性炎症破坏。骨科手术期间预防骨髓炎很有必要。NFκB必需调节因子结合域(NBD)肽是IκB激酶复合物的细胞穿透性肽抑制剂。NBD肽在缓解骨髓炎炎症和抑制骨缺损方面的预防作用仍在研究中。我们的目的是确定NBD肽对骨髓炎感染诱导的骨缺损的预防作用。

方法

本研究使用骨髓炎兔模型。将兔子分为四组:NBD组、头孢唑林组、对照组和PBS组。评估红细胞沉降率、CRP和TNFα水平的临床和实验室指标以监测全身反应。通过放射学、组织学和微生物学检查、免疫组织化学、免疫荧光和微型CT扫描评估NBD肽在诱导的骨髓炎中的疗效。

结果

总体而言,与对照组相比,NBD肽有效减轻了兔子的临床症状。X线摄影显示细菌感染对照组的骨髓炎更严重。头孢唑林组和NBD组的平均评分之间没有显著差异。病变切片的组织学结果进一步证实了各组之间的不同严重程度。此外,头孢唑林组和NBD组之间存在显著的病理差异,PBS组没有明显的病理变化。

结论

对骨缺损区域预防性给予NBD肽可抑制细菌扩散并促进骨再生,使NBD肽成为预防骨感染的一种可能的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a89/9059993/ca4b0d4e0fba/JIR-15-2745-g0001.jpg

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