二甲双胍增加促炎细胞因子的表达并抑制冈上肌脂肪浸润。
Metformin increases the expression of proinflammatory cytokines and inhibits supraspinatus fatty infiltration.
机构信息
Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
Department of Orthopaedic Surgery, School of Medicine, Konkuk University Medical Center, Seoul, Korea.
出版信息
J Orthop Surg Res. 2023 Sep 12;18(1):674. doi: 10.1186/s13018-023-04163-z.
BACKGROUND
After a rotator cuff (RC) tendon tear, the supraspinatus (SS) inflammatory response induces fatty infiltration (FI). Metformin has the effect of regulating the initial inflammatory response of atrophic muscles. Therefore, this study aimed to investigate the effect of metformin use on modulating the expression of proinflammatory cytokines and SS FI in an acute RC tear rat model.
METHODS
This study used 26 male Sprague-Dawley rats. Animals were randomly divided into two groups: The metformin group received metformin for 5 days after cutting the RC tendon, and the control group was administered only with saline after cutting the tendon. Metformin 50 mg/kg was intraperitoneally injected for 5 days. Three rats in each group were sacrificed 5 days after SS tendon rupture surgery, and 10 rats in each group were sacrificed 14 days after surgery. The SS was sampled 5 days after SS tendon tear surgery, and the expression of proinflammatory cytokines was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). On day 14 after sampling, histological analysis of the SS was performed using hematoxylin and eosin, Masson's trichrome, and picrosirius red staining.
RESULTS
On day 5 of surgery, the expression values of interferon gamma (increased 7.2-fold, P < .01), tumor necrosis factor alpha (increased 13-fold, P < .05), interleukin-1β (increased 4.7-fold, P < .001), and interleukin-6 (increased 4.6-fold, P < .01) increased significantly in the metformin group compared with those in the control group. As a result of Oil Red O staining, SS FI was significantly suppressed in the metformin group compared with that in the control group (metformin group, 305 ± 50.3 µm, P < .001; control group, 3136 ± 662.8 µm, P < .001). In addition, the SS volume of the metformin group was not reduced compared with those of the control group, and the morphology and structure of the SS were better preserved.
CONCLUSIONS
The results of this study revealed that metformin can increase the expression of proinflammatory cytokines and suppress SS fat infiltration in delayed sutures.
背景
肩袖撕裂（RC）后，冈上肌（SS）的炎症反应会引起脂肪浸润（FI）。二甲双胍具有调节萎缩肌肉初始炎症反应的作用。因此，本研究旨在探讨二甲双胍在急性 RC 撕裂大鼠模型中对调节促炎细胞因子表达和 SS FI 的影响。
方法
本研究使用 26 只雄性 Sprague-Dawley 大鼠。动物随机分为两组：二甲双胍组在切断 RC 肌腱后 5 天内给予二甲双胍，对照组仅在切断肌腱后给予生理盐水。连续 5 天腹腔注射 50mg/kg 二甲双胍。每组各有 3 只大鼠在 SS 肌腱断裂手术后 5 天被处死，每组各有 10 只大鼠在手术后 14 天被处死。在 SS 肌腱撕裂手术后 5 天取样 SS，通过定量逆转录聚合酶链反应（qRT-PCR）测量促炎细胞因子的表达。在取样后 14 天，使用苏木精和伊红、Masson 三色和苦味酸天狼猩红染色对 SS 进行组织学分析。
结果
手术后第 5 天，与对照组相比，二甲双胍组干扰素γ（增加 7.2 倍，P <.01）、肿瘤坏死因子-α（增加 13 倍，P <.05）、白细胞介素-1β（增加 4.7 倍，P <.001）和白细胞介素-6（增加 4.6 倍，P <.01）的表达值显著升高。通过油红 O 染色，与对照组相比，二甲双胍组 SS FI 显著受到抑制（二甲双胍组，305 ± 50.3 µm，P <.001；对照组，3136 ± 662.8 µm，P <.001）。此外，与对照组相比，二甲双胍组 SS 体积未减少，SS 的形态和结构得到更好的保留。
结论
本研究结果表明，二甲双胍可增加促炎细胞因子的表达，抑制延迟缝合时 SS 的脂肪浸润。
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