Abstract: Objective Across sectional study was undertaken to investigate the related mechanism of ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS).Methods Twenty-four diabetes mellitus patients [DM (+)]and twenty normoglycemic patients [DM (-)]with LSCS were enrolled in this study. Sorbitol in LF was analyzed using D-Sorbitol/Xylitol test kit. The thickness of LF was measured by CT. The structure of LF was observed after HE and Masson’s trichrome staining. The cell cycle and proliferation of fibroblastic cell NIH3T3 line cultured in high glucose was analyzed. Sorbitol of NIH3T3 was detected under different backgrounds in vitro, normal glucose, high glucose and high glucose burdened with aldose reductase inhibitor(ARI), Epalrestat. The expressions of inflammatory factors were detected by qPCR and Western-blot under above different backgrounds. Results LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β and of CD68-positive staining than that of the normoglycemic subjects( P<0.01). The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor( P<0.05). Conclusions Sorbitol level of the LF is significantly increased in the DM patients with LSCS. Increased sorbitol recruites inflammatory factors and fibrogenic-related factor TGF-β in LF of DM patients with LSCS which contributes to the LF hypertrophy.

Key words: sorbitol, diabetes mellitus, aldose reductase inhibitor, lumbar spinal canal stenosis, ligamentum flavum