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氨甲环酸与万古霉素联合治疗对人软骨细胞的体外影响?

Does Combined Treatment with Tranexamic Acid and Vancomycin Affect Human Chondrocytes In Vitro?

作者信息

Wagenbrenner Mike, Heinz Tizian, Anderson Philip M, Stratos Ioannis, Arnholdt Joerg, Mayer-Wagner Susanne, Horas Konstantin, Docheva Denitsa, Holzapfel Boris M, Rudert Maximilian, Weißenberger Manuel

机构信息

Department of Orthopaedic Surgery and Musculoskeletal Tissue Regeneration, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074 Wuerzburg, Germany.

Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, 81377 Munich, Germany.

出版信息

Pharmaceuticals (Basel). 2024 Nov 24;17(12):1576. doi: 10.3390/ph17121576.

Abstract

The aim of our study was to examine the combined effects of tranexamic acid (TXA) and vancomycin powder (VP) on chondrocytes in vitro. Despite the use of TXA and VP being linked to a reduced risk of extensive postoperative blood loss and periprosthetic joint infections (PJIs) in TKA, the possible cytotoxic side effects on periarticular cell types remain unclear. Human chondrocytes were harvested from hyaline cartilage and expanded in monolayer culture before being simultaneously exposed to different concentrations of TXA and VP for varying exposure times. Cell viability and proliferation were assessed using an ATP assay and an Annexin 5 assay, respectively, while changes in the relative expression of chondrogenic marker genes were examined using semiquantitative RT-PCR. The simultaneous exposure of chondrocytes to TXA and VP for more than 48 h led to a reduction in both cell viability and proliferation rates. When exposing chondrocytes to the lowest examined concentrations of both TXA (10 mg/mL) and VP (3 mg/mL), the observed effects were delayed until 96 h. However, our study found no dependencies of the observed effects on the concentrations tested. Further, we found no effects on the expression of chondrogenic marker genes. Consequently, limiting the exposure time of chondrocytes to TXA and VP in an in vitro setting to 24 h may be considered safe and could help to further improve the understanding of the safe use of substances in vivo. However, further in vitro research is required to develop a comprehensive understanding of the effects of both VP and TXA on important periarticular cell types in TKA, including chondrocytes, osteocytes, and tenocytes.

摘要

我们研究的目的是在体外研究氨甲环酸(TXA)和万古霉素粉末(VP)对软骨细胞的联合作用。尽管在全膝关节置换术(TKA)中使用TXA和VP与降低广泛术后失血和假体周围关节感染(PJI)的风险有关,但对关节周围细胞类型可能的细胞毒性副作用仍不清楚。从透明软骨中获取人软骨细胞,在单层培养中扩增,然后同时暴露于不同浓度的TXA和VP中,暴露时间不同。分别使用ATP检测法和膜联蛋白5检测法评估细胞活力和增殖情况,同时使用半定量逆转录聚合酶链反应(RT-PCR)检测软骨生成标记基因相对表达的变化。软骨细胞同时暴露于TXA和VP超过48小时会导致细胞活力和增殖率降低。当将软骨细胞暴露于TXA(10毫克/毫升)和VP(3毫克/毫升)的最低检测浓度时,观察到的效应延迟至96小时。然而,我们的研究发现观察到的效应与所测试的浓度无关。此外,我们发现对软骨生成标记基因的表达没有影响。因此,在体外将软骨细胞暴露于TXA和VP的时间限制在24小时可能被认为是安全的,这有助于进一步提高对体内物质安全使用的理解。然而,需要进一步的体外研究来全面了解VP和TXA对TKA中重要关节周围细胞类型(包括软骨细胞、骨细胞和肌腱细胞)的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8784/11677089/ee03bd6b024e/pharmaceuticals-17-01576-g003.jpg

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