Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress.

ABSTRACT

PURPOSE: Diabetic neuropathy (DN) is a notable complication of diabetes mellitus. The potential involvement of miR-146a in DN regulation is presently under investigation. Metformin, a commonly prescribed medication for diabetes, is the primary therapeutic intervention. This study aimed to unveil the potential protective effects of metformin on diabetic neuropathy and explore the mechanisms underlying its action. METHOD: Six-weeks male Sprague Dawley rats (n = 40) were randomly divided into 5 groups. The rat model of diabetic neuropathy (DN) was established by administering streptozotocin (STZ). To investigate the effects on the sciatic nerve and resident Schwann cells (RSCs), metformin and miR-146a mimics were administered, and our research explored the potential underlying mechanism. RESULT: The sciatic nerve samples obtained from diabetic rats exhibited noticeable morphological damage, accompanied by decreased miR-146a expression (2.61 ± 0.11 vs 5.0 ± 0.3, p < 0.01) and increased inflammation levels (p65 1.89 ± 0.04 vs 0.82 ± 0.05, p < 0.01; TNF-α 0.93 ± 0.03 vs 0.33 ± 0.03, p < 0.01). Notably, the administration of metformin effectively ameliorated the structural alterations in the sciatic nerve by suppressing the inflammatory pathway (p65 1.15 ± 0.05 vs 1.89 ± 0.04, p < 0.01; TNF-α 0.67 ± 0.04 vs 0.93 ± 0.03, p < 0.01) and reducing oxidative stress (NO 0.062 ± 0.004 vs 0.154 ± 0.004umol/mg, p < 0.01; SOD 3.08 ± 0.09 vs 2.46 ± 0.09 U/mg, p < 0.01). The miR-146a mimics intervention group exhibited comparable findings. CONCLUSION: This study's findings implied that metformin can potentially mitigate diabetic neuropathy in rats through the modulation of miR-146a expression.