The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

ABSTRACT

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.