糖尿病を合併した腰部脊柱管狭窄症(狭窄症), および非合併の狭窄症手術例における黄色靭帯のソルビトール濃度は, 有意に糖尿病群でソルビトールが上昇していた。通常のグルコース濃度, 高グルコース濃度で培養を行ったNTH3T3の細胞内のソルビトール含有量は, 高グルコース濃度で有意に高値であった。さらに, このソルビトール量はアルドース還元酵素阻害剤の添加により, 有意に減少した。炎症性サイトカインやpro-fibrotic factors1のmRNAsの発現は, 糖尿病を合併例の黄色靱帯で有意に上昇していた。NIH3T3細胞のWesternブロットによる解析でも同様の結果が出た。
The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts.
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