腺苷、利多卡因和镁疗法可促进实验性前十字韧带断裂和重建后的关节组织愈合。

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING
Jodie L Morris, Hayley L Letson, Peter C McEwen, Geoffrey P Dobson
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引用次数: 0

摘要

目的:腺苷、利多卡因和Mg2+(ALM)疗法在前交叉韧带(ACL)重建(ACLR)术后早期对男性和女性产生不同的免疫炎症反应。我们的目的是研究ALM疗法对术后28天关节组织修复和恢复的性别特异性影响:雄性(n = 21)和雌性(n = 21)成年 Sprague-Dawley 大鼠被随机分为 ALM 或生理盐水对照治疗组。前交叉韧带断裂三天后,动物接受前交叉韧带重建术。在切开皮肤前开始静脉注射 ALM 或生理盐水,并持续一小时。在皮肤缝合之前,还在动物关节内注入 ALM 或生理盐水。对动物进行为期 28 天的监测,评估关节功能、疼痛、炎症指标、组织病理学和组织修复指标:结果:尽管雄性动物的膝关节功能相当,但与对照组相比,经 ALM 治疗的动物全身炎症、滑膜液血管生成和促炎介质、滑膜炎和脂肪垫纤维化变化均有所减轻。在前交叉韧带移植物中,经 ALM 治疗的男性组织修复标志物表达增加,炎症减少,胶原组织增加,移植物-骨愈合得到改善。与男性相比,女性没有持续性全身炎症的迹象。与对照组相比,经 ALM 治疗的女性膝关节伸展性和步态生物力学得到改善,滑膜巨噬细胞炎症蛋白-1 α(MIP-1α)升高。在前交叉韧带移植物中,经 ALM 治疗的女性炎症减少,胶原组织增加,移植物-骨愈合得到改善。在接受ALM治疗的动物关节软骨中,雄性动物的基质金属蛋白酶(MMP)-13表达减弱,而雌性动物的修复标志物则有所增加:28天后,ALM疗法能以性别特异性的方式减轻炎症、增强组织修复模式并改善关节功能。该研究支持向人体安全性试验过渡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adenosine, lidocaine, and magnesium therapy augments joint tissue healing following experimental anterior cruciate ligament rupture and reconstruction.

Aims: Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods: Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.

Results: Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased.

Conclusion: At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials.

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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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