Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America.
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America.
PLoS One. 2021 Jan 22;16(1):e0245594. doi: 10.1371/journal.pone.0245594. eCollection 2021.
While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.
虽然肥胖和胰岛素抵抗是全关节置换术后（TJA）伤口并发症的已知危险因素，但生物学原因仍有待阐明。最近，中性粒细胞胞外诱捕网（NETosis）的形成被确定为胰岛素抵抗状态下延迟伤口愈合的介质。在此，我们探讨了 TJA 患者肥胖、胰岛素抵抗与 NET 形成生物标志物之间的关系。我们纳入了 14 名肥胖（BMI≥30kg/m2）和 15 名体重正常（BMI<30kg/m2）的患者，他们接受了膝关节或髋关节初次 TJA。在手术当天，采集手术关节近端的骨骼肌和血浆。通过免疫印迹法评估骨骼肌中 NETosis 生物标志物精氨酸脱氨酶 4（PAD4）和中性粒细胞弹性蛋白酶（NE）的蛋白丰度，并评估血浆中的代谢参数（葡萄糖、胰岛素、甘油三酯、游离脂肪酸）和无细胞双链 DNA（cf-dsDNA），并将其与肥胖和胰岛素抵抗（用胰岛素抵抗的稳态模型评估来衡量）相关联。在比较瘦和肥胖患者时，血浆 cf-dsDNA 或骨骼肌 NE 或 PAD4 丰度没有差异。相比之下，骨骼肌 PAD4 丰度与胰岛素抵抗呈正相关，但与 NE 或血浆 cf-dsDNA 无关。与胰岛素敏感的 TJA 患者相比，胰岛素抵抗的 TJA 患者在手术部位的 PAD4 表达更高，因此可能具有更高的 NET 形成率，这可能导致手术部位伤口愈合延迟。
