Jeffs Alexander D, Boyd Michael, Larabee Landon, Shelton Matthew, Bassil Alexander, Taylor Ross, Berkoff David
Department of Orthopaedics, The University of North Carolina, Chapel Hill, NC, USA.
Department of Family Medicine, The University of North Carolina, Chapel Hill, NC, USA.
J Exp Orthop. 2023 Jun 21;10(1):64. doi: 10.1186/s40634-023-00616-w.
Arthrofibrosis is a common inflammatory complication of joint trauma and surgery. 5lipoxygenase (5-LO) is a key enzyme involved in inflammation. Inhibition of 5-LO has been shown to reduce inflammation in heart and lung models but has not been examined in a joint contracture model.
Twenty-six rats underwent joint contracture. Six rats served as non-surgical controls. A 5-LO inhibitor, caffeic acid (CA), suspended in 10% ethanol was orally administered to 14 rats and ethanol without CA to the remaining 12 rats daily for 21 days. Leukotriene B4 (LTB4) levels were measured, both systemically and locally. 5-LO levels in the posterior capsule were quantified by measuring the ratio of the length of the posterior capsule demonstrating 5-LO immunostaining to the total length of the capsule.
Joint contracture was successfully achieved in all rats who underwent manipulation. Levels of 5- LO measured in the posterior capsule were significantly increased in the animals who underwent surgery (56%/44-64) compared to the non-surgical control animals (7%/4-9). LTB4 levels were found to be significantly lower in the non-surgical control animals (107.79 ± 34.08 pg/ml) compared to all surgical animals (157.6 ± 55.3 pg/ml).
Surgical intervention resulted in increased 5-LO activity of the synovial surface of the posterior capsule and increased LTB4 levels in the patellar tendon-fat pad. Oral administration of the 5LO inhibitor, CA, was ineffective at reducing systemic and local LTB4 levels and preventing knee joint contracture. Inhibiting 5-LO activity may still be effective in preventing arthrofibrosis and warrants further investigation.
关节纤维化是关节创伤和手术常见的炎症并发症。5-脂氧合酶（5-LO）是参与炎症反应的关键酶。在心脏和肺部模型中，抑制5-LO已被证明可减轻炎症，但尚未在关节挛缩模型中进行研究。
26只大鼠接受关节挛缩手术。6只大鼠作为非手术对照。14只大鼠每日口服悬浮于10%乙醇中的5-LO抑制剂咖啡酸（CA），其余12只大鼠每日口服不含CA的乙醇，持续21天。测量全身和局部的白三烯B4（LTB4）水平。通过测量后关节囊显示5-LO免疫染色的长度与关节囊总长度的比值，对后关节囊中的5-LO水平进行定量。
所有接受手术的大鼠均成功实现关节挛缩。与非手术对照动物（7%/4-9）相比，接受手术的动物后关节囊中测得的5-LO水平显著升高（56%/44-64）。发现非手术对照动物的LTB4水平（107.79±34.08 pg/ml）显著低于所有手术动物（157.6±55.3 pg/ml）。
手术干预导致后关节囊滑膜表面的5-LO活性增加，髌腱-脂肪垫中的LTB4水平升高。口服5-LO抑制剂CA在降低全身和局部LTB4水平以及预防膝关节挛缩方面无效。抑制5-LO活性在预防关节纤维化方面可能仍然有效，值得进一步研究。
