Metformin increases the expression of proinflammatory cytokines and inhibits supraspinatus fatty infiltration

Abstract

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 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.

Conclusions: The results of this study revealed that metformin can increase the expression of proinflammatory cytokines and suppress SS fat infiltration in delayed sutures.

Keywords: Fatty infiltration; Histology; Inflammatory response; Metformin; Rotator cuff tear; Supraspinatus atrophy.