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抗逆转录病毒疗法对骨折愈合的影响:一项体内动物模型研究。

The effect of anti-retroviral therapy on fracture healing : an in vivo animal model.

作者信息

Graham Simon M, Jalal Murtadhah M K, Lalloo David G, Hamish R W Simpson A

机构信息

Oxford Trauma and Emergency Care, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Liverpool Orthopaedic and Trauma Service, Department of Orthopaedic and Trauma Surgery, Liverpool University Hospital Foundation Trust, Liverpool, UK.

出版信息

Bone Joint Res. 2022 Aug;11(8):585-593. doi: 10.1302/2046-3758.118.BJR-2021-0523.R2.

Abstract

AIMS

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

METHODS

A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.

RESULTS

The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups.

CONCLUSION

This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion.Cite this article:  2022;11(8):585-593.

摘要

目的

多种抗逆转录病毒疗法(ART)被认为可能与HIV相关骨病有关。本研究旨在评估联合抗逆转录病毒疗法对骨折愈合过程的影响。

方法

将16只成年雄性Wistar大鼠随机分为两组(每组n = 8只):第1组每天口服替诺福韦30毫克、拉米夫定30毫克和依非韦伦60毫克的组合,而第2组用作对照。在进行一周的药物预负荷后,所有大鼠均接受了标准化的胫骨干中段截骨手术,采用髓内钉固定,骨折部位无间隙。定期监测骨折愈合进展,持续8周。在安乐死后,通过显微CT、力学和组织学进行进一步评估。两名不知情的骨科医生使用胫骨放射学会评分系统(RUST)来确定骨折愈合情况。

结果

术后第4周,两组的骨折愈合过程有所不同;第1组(接受抗逆转录病毒疗法治疗)的8只大鼠中只有2只显示完全愈合,而第2组(对照组)的8只大鼠中有7只实现了骨愈合(p = 0.040)。然而,术后第8周,骨愈合情况无统计学差异;两组的8只大鼠中有7只进展为完全愈合。

结论

本研究表明,联合抗逆转录病毒疗法导致大鼠术后第4周骨折愈合延迟,但未导致骨不连的发生。引用本文:2022;11(8):585-593。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa93/9396923/d53384c2ef51/BJR-11-585-g0001.jpg

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