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氨甲环酸可减轻小鼠创伤性骨关节炎的进展。

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

机构信息

Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Am J Sports Med. 2024 Mar;52(3):766-778. doi: 10.1177/03635465231220855. Epub 2024 Feb 2.

DOI:10.1177/03635465231220855
PMID:38305280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10905980/
Abstract

BACKGROUND

Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression.

PURPOSE

To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice.

STUDY DESIGN

Controlled laboratory study.

METHODS

OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro-computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically.

RESULTS

Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed.

CONCLUSION

Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery.

CLINICAL RELEVANCE

TXA might be beneficial in patients with posttraumatic OA of the knee.

摘要

背景

创伤后骨关节炎(OA)是一种常见的疾病,与高社会经济负担有关,尤其是在年轻、活跃和工作的患者中。氨甲环酸(TXA)在骨科创伤手术中常被用作抗纤维蛋白溶解剂来控制过度出血。先前的研究报告称,TXA 可调节炎症和骨细胞功能,这两者在创伤后 OA 疾病进展过程中都失调。

目的

评估全身和局部 TXA 治疗对小鼠膝关节创伤后 OA 进展的治疗效果。

研究设计

对照实验室研究。

方法

通过前交叉韧带(ACL)切断术在雌性小鼠的右膝关节诱导 OA。从手术当天开始,每天通过腹腔内或每周通过关节内注射 TXA 或载体治疗 4 周。通过组织学评分评估关节软骨退变、滑膜炎、骨侵蚀和骨赘形成。通过微计算机断层扫描评估评估软骨下骨微观结构和骨赘体积。通过组织形态计量学评估评估软骨厚度和骨重塑。

结果

全身和局部 TXA 治疗均显著降低了创伤后 OA 的软骨退变、滑膜炎和骨侵蚀评分,并增加了透明软骨与钙化软骨厚度的比值。全身 TXA 逆转了 ACL 切断术引起的软骨下骨丢失和骨赘形成,而局部治疗则没有效果。全身 TXA 减少了破骨细胞的数量和表面积,而对成骨细胞没有影响。局部 TXA 对成骨细胞或破骨细胞参数没有影响。

结论

全身和局部 TXA 对创伤后 OA 的进展都有保护作用。因此,TXA 的药物再利用可能对创伤后 OA 的预防或治疗有用,特别是在 ACL 手术后。

临床相关性

TXA 可能对膝关节创伤后 OA 的患者有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/a28d426a2c87/10.1177_03635465231220855-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/42fbe0935c69/10.1177_03635465231220855-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/0555351249cf/10.1177_03635465231220855-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/9dba2c2a437d/10.1177_03635465231220855-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/bb383830dccb/10.1177_03635465231220855-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/181bb3b95735/10.1177_03635465231220855-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/a28d426a2c87/10.1177_03635465231220855-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/42fbe0935c69/10.1177_03635465231220855-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/0555351249cf/10.1177_03635465231220855-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/9dba2c2a437d/10.1177_03635465231220855-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/bb383830dccb/10.1177_03635465231220855-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/181bb3b95735/10.1177_03635465231220855-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/087e/10905980/a28d426a2c87/10.1177_03635465231220855-fig6.jpg

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