Department of Orthopaedic Surgery, Juntendo University Urayasu Hospital, Chiba, Japan.
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Am J Sports Med. 2023 May;51(6):1596-1607. doi: 10.1177/03635465231160772. Epub 2023 Apr 5.
Oxidative stress inhibits tendon-to-bone healing after rotator cuff repair. Regulation of oxidative stress has the potential to accelerate this healing, but its mechanism remains unclear.
To investigate the effects of reducing oxidative stress by applying antioxidants, such as -acetylcysteine (NAC) and vitamin C (VC), on rotator cuff repair in a rat rotator cuff repair model.
Controlled laboratory study.
A total of 48 Sprague Dawley rats underwent bilateral surgery to repair the infraspinatus tendon to its insertion site 1 week after detachment. Rats were assigned to either the NAC group, the VC group, or a control group. Histological evaluation was performed via hematoxylin-eosin or toluidine blue staining, and oxidative stress was assessed via dihydroethidium intensity and protein carbonyl concentration at 3 and 6 weeks. Superoxide dismutase 1 (SOD1), SOD2, SOD3, peroxiredoxin 5, collagen type I (COL1), COL3, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 expression and SOD activity were determined at 3 and 6 weeks. Biomechanical tests were performed at 6 and 12 weeks.
Histological evaluation showed that the number of chondrocytes in the NAC group at 6 weeks and in the VC group at 3 and 6 weeks, the area of fibrocartilage at 6 weeks in the VC group, and collagen fibers at 6 weeks in the NAC and VC groups were significantly increased compared with those in the control group. Dihydroethidium intensity at 3 and 6 weeks and protein carbonyls at 6 weeks in the NAC and VC groups were significantly decreased. SOD1 expression and SOD activity at 3 weeks in the VC group and peroxiredoxin 5 expression at 6 weeks in the NAC group were significantly upregulated compared with that in the control group. COL3 expression was significantly upregulated at 6 weeks in the VC group, and MMP-13 expression was significantly decreased at 6 weeks in the NAC and VC groups. The biomechanical strength showed no significant difference.
Antioxidant treatment, via NAC or VC administration, reduced oxidative stress in the rotator cuff repair site and accelerated healing.
These findings provide essential indications to develop clinical strategies for improved healing after rotator cuff surgical repair in patients.
氧化应激会抑制肩袖修复后的腱骨愈合。调节氧化应激有可能加速这种愈合，但具体机制尚不清楚。
通过应用抗氧化剂（如乙酰半胱氨酸[NAC]和维生素 C[VC]）来减少氧化应激，从而在大鼠肩袖修复模型中研究其对肩袖修复的影响。
对照实验室研究。
48 只 Sprague Dawley 大鼠在分离后 1 周内行双侧手术将冈下肌腱修复至其插入部位。将大鼠分为 NAC 组、VC 组或对照组。通过苏木精-伊红或甲苯胺蓝染色进行组织学评估，并在 3 周和 6 周时通过二羟乙基荧光素强度和蛋白质羰基浓度评估氧化应激。在 3 周和 6 周时测定超氧化物歧化酶 1（SOD1）、SOD2、SOD3、过氧化物酶 5、胶原 I（COL1）、COL3、基质金属蛋白酶 1（MMP-1）、MMP-3 和 MMP-13 的表达和 SOD 活性。在 6 周和 12 周时进行生物力学测试。
组织学评估显示，NAC 组在 6 周时的软骨细胞数量和 VC 组在 3 周和 6 周时的纤维软骨面积、VC 组在 6 周时的胶原蛋白纤维均明显高于对照组。NAC 和 VC 组在 3 周和 6 周时的二羟乙基荧光素强度和 6 周时的蛋白质羰基含量均明显降低。VC 组在 3 周时的 SOD1 表达和 SOD 活性以及 NAC 组在 6 周时的过氧化物酶 5 表达均明显高于对照组。VC 组在 6 周时 COL3 表达明显上调，NAC 和 VC 组在 6 周时 MMP-13 表达明显下调。生物力学强度无显著差异。
通过 NAC 或 VC 给药进行抗氧化治疗可减少肩袖修复部位的氧化应激并加速愈合。
这些发现为开发改善肩袖手术后患者愈合的临床策略提供了重要依据。
