二甲双胍 (Metformin) 增加了前炎性细胞因子的表达并抑制了肩胛骨上肌肉脂肪浸润。
Metformin increases the expression of proinflammatory cytokines and inhibits supraspinatus fatty infiltration.
发表日期:2023 Sep 12
作者:
Jong Pil Yoon, Sung-Jin Park, Dong-Hyun Kim, Seok Won Chung
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
在旋转肌袖(RC)肌腱撕裂后,冈上肌(SS)的炎症反应引起了脂肪浸润(FI)。二甲双胍具有调节肌肉萎缩初期炎症反应的作用。因此,本研究旨在调查二甲双胍在急性RC肌腱撕裂大鼠模型中对调节前炎症因子和SS脂肪浸润的影响。本研究使用了26只雄性Sprague-Dawley大鼠。动物随机分为两组:二甲双胍组在切割RC肌腱后连续用药5天,对照组仅注射生理盐水。二甲双胍每次剂量为50mg/kg,每天腹腔注射一次,持续用药5天。两组各有3只大鼠在SS肌腱断裂手术后5天牺牲,每组有10只大鼠在手术后14天牺牲。在SS肌腱撕裂手术后5天,取样SS,用定量逆转录聚合酶链式反应(qRT-PCR)测定前炎症细胞因子的表达。在取样后的第14天,用苏木精伊红染色、麦氏三色染色和产碱红染色对SS进行组织学分析。在手术的第5天,与对照组相比,二甲双胍组干扰素γ(增加7.2倍,P < 0.01)、肿瘤坏死因子α(增加13倍,P < 0.05)、白细胞介素-1β(增加4.7倍,P < 0.001)和白细胞介素-6(增加4.6倍,P < 0.01)的表达值显著增加。利用Oil Red O染色进行分析显示,与对照组相比,二甲双胍组的SS脂肪浸润明显减少(二甲双胍组,305 ± 50.3 µm2,P < 0.001;对照组,3136 ± 662.8 µm2,P < 0.001)。此外,二甲双胍组的SS体积与对照组相比没有减少,且SS的形态和结构得到较好的保留。本研究结果显示,二甲双胍可以增加前炎症细胞因子的表达,并抑制延迟缝合中SS的脂肪浸润。© 2023. BioMed Central Ltd., part of Springer Nature.
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.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.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 µm2, P < .001; control group, 3136 ± 662.8 µm2, 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.The results of this study revealed that metformin can increase the expression of proinflammatory cytokines and suppress SS fat infiltration in delayed sutures.© 2023. BioMed Central Ltd., part of Springer Nature.