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万古霉素和庆大霉素抗生素对人成骨细胞增殖、代谢功能及骨矿化的影响。

The Effect of Vancomycin and Gentamicin Antibiotics on Human Osteoblast Proliferation, Metabolic Function, and Bone Mineralization.

作者信息

Philp Ashleigh M, Raja Saroop, Philp Andrew, Newton Ede Matthew P, Jones Simon W

机构信息

MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, Queen Elizabeth Hospital, University of Birmingham, Birmingham, United Kingdom.

The Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Northfield, Birmingham, United Kingdom.

出版信息

Spine (Phila Pa 1976). 2017 Feb;42(3):202-207. doi: 10.1097/BRS.0000000000001712.

Abstract

STUDY DESIGN

The present study investigates the effect of vancomycin and gentamicin antibiotics on primary human osteoblasts. Osteoblasts were incubated with vancomycin, gentamicin, or with povidone-iodine (PVI), at concentrations advocated for wound irrigation. Osteoblast proliferation, metabolic function, and bone mineralization were measured.

OBJECTIVE

The aim of the study was to model gentamicin and vancomycin wound irrigation in vitro and to examine the effect on osteoblast viability and cellular function in comparison to 0.35% PVI.

SUMMARY OF BACKGROUND DATA

Vancomycin, gentamicin, and dilute PVI are employed as wound irrigants in spinal surgery to reduce infection. We have, however, recently demonstrated that 0.35% PVI has a detrimental effect on osteoblast cellular function and bone mineralization. Studies to determine the effects of antibiotic wound irrigation solutions on osteoblasts and bone mineralization are therefore warranted.

METHODS

Primary human osteoblasts were exposed for 20 minutes to phosphate buffered saline (PBS) control, vancomycin (35 or 3.5 mmol/L), gentamicin (34 or 3.4 mmol/L), or 0.35% PVI for 3 minutes. Cellular proliferation was measured during 7 days by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Osteoblast metabolic function was determined using a Seahorse XFe24 Bioanalyzer. Mineralized bone nodules were quantified using Alizarin red.

RESULTS

At concentrations advocated for wound irrigation, both gentamicin (3.4 mmol/L) and vancomycin (3.5 mmol/L) induced a transient 15% to 20% reduction in osteoblast proliferation, which returned to control values within 72 hours. This was in marked contrast to the effect of 0.35% PVI, which resulted in a sustained reduction in osteoblast proliferation of between 40% and 50% during 7 days. Neither gentamicin nor vancomycin at concentrations up to 10× clinical dose had any effect on osteoblast oxygen consumption rate, or significantly affected mineralized bone nodule formation.

CONCLUSION

Vancomycin and gentamicin solutions, at concentrations advocated for intrawound application in spinal surgery, have a small but transient effect on osteoblast proliferation, and no effect on either osteoblast metabolic function or bone nodule mineralization.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

本研究调查了万古霉素和庆大霉素抗生素对原代人成骨细胞的影响。将成骨细胞与万古霉素、庆大霉素或聚维酮碘(PVI)以伤口冲洗推荐浓度进行孵育。测量成骨细胞增殖、代谢功能和骨矿化情况。

目的

本研究旨在体外模拟庆大霉素和万古霉素伤口冲洗,并与0.35% PVI相比,研究其对成骨细胞活力和细胞功能的影响。

背景数据总结

万古霉素、庆大霉素和稀释后的PVI在脊柱手术中用作伤口冲洗剂以减少感染。然而,我们最近证明0.35% PVI对成骨细胞功能和骨矿化有不利影响。因此,有必要开展研究以确定抗生素伤口冲洗液对成骨细胞和骨矿化的影响。

方法

将原代人成骨细胞暴露于磷酸盐缓冲盐水(PBS)对照、万古霉素(35或3.5 mmol/L)、庆大霉素(34或3.4 mmol/L)或0.35% PVI中20分钟(PVI为3分钟)。在7天内通过MTS(3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑)法测量细胞增殖。使用海马XFe24生物分析仪测定成骨细胞代谢功能。使用茜素红对矿化骨结节进行定量。

结果

在伤口冲洗推荐浓度下,庆大霉素(3.4 mmol/L)和万古霉素(3.5 mmol/L)均导致成骨细胞增殖短暂降低15%至20%,并在72小时内恢复至对照值。这与0.35% PVI的作用形成显著对比,后者导致成骨细胞增殖在7天内持续降低40%至50%。浓度高达临床剂量10倍的庆大霉素和万古霉素均对成骨细胞耗氧率无任何影响,也未显著影响矿化骨结节形成。

结论

在脊柱手术伤口内应用推荐浓度的万古霉素和庆大霉素溶液对成骨细胞增殖有轻微但短暂的影响,对成骨细胞代谢功能或骨结节矿化无影响。

证据水平

无。

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