The Effect Of Dioscin From The Extract Of Dioscorea Nigra On The Nrf2/HO-1 Pathway Of The Sciatic Nerve In PDPN Mice

Purpose: To investigate the effect of dioscin from the extract of Discorea nipponica Makino on the anti-oxidative stress pathway in the model mice of painful diabetic peripheral neuropathy.It provides a deep theoretical basis for the clinical treatment of painful diabetic peripheral neuropathy.Methods: Using random number table method,12 out of 83 SPF male C57 BL / 6 mice were randomly selected as the normal group(CON),and the rest were used as a model.The model was fed on a high-fat diet for 8 weeks,and intraperitoneal injection of streptozotocin(STZ)for 2 consecutive days 70 mg / kg.The mice whose blood glucose was higher than 16.7mmol / l were included in the follow-up study,and they were fed with common feed for 6 weeks.After 6 weeks,the mice whose mechanical pain threshold decreased by 50% were successfully modeled.The mice successfully modeled were randomly divided into model group(DM),low-dose dioscin group(DIO50)(52.26 mg / kg),high-dose dioscin group(DIO100)(104.52 mg / kg),and Alpha-lipoic acid group(ALA)(100mg / kg).Treatment continued for 8 weeks.During the experiment,the behavioral state of mice was observed and blood glucose and body weight were monitored dynamic.The behavioral effects of dioscin were detected by hot tail immersion test and paw tactile response.The levels of Nrf2,HO-1 and NQO1 were detected by immunofluorescence and Western blot.Statistical analysis was done using SPSS,and P<0.05 was considered statistically significant.Results: 1.The mice in the model group had poor mental state,heavy odor,slow movement,dry and dull hair,and appeared to drink,eat,and urinate with weight loss.After 8 weeks,the mice in the treatment group all showed the above symptoms,but the symptoms were reduced compared with the model group.2.Compared with the control group,the blood glucose level of the model group increased significantly(P <0.01).After 8 weeks of treatment,the blood glucose level of the treatment group mice significantly decreased compared with the model group(P <0.01)and the high dose group was lower than that of alpha-lipoic acid group(P <0.01).3.Compared with the control group,the weight of the model group decreased significantly(P <0.01).After 8 weeks of treatment,the weight of the treatment group mice increased significantly compared with the model group(P <0.01).And the dioscin treatment group compared with alpha-lipoic acid group,it was statistically significant(P < 0.05).4.Compared with the control group,the tail-flick latency of the model group was significantly reduced(P <0.01).The tail-flick latency of the treatment group was significantly increased compared with the model group at 4 and 8 weeks(P <0.01).There was no statistical difference between the high-dose group and the alpha-lipoic acid group.Compared with the control group,the mechanical pain threshold was significantly reduced(P <0.01).At 4 and 8 weeks,the pain threshold was significantly increased in the treatment group compared with the model group(P <0.01).There was no statistical difference between the dioscin-treated group and the alpha-lipoic acid group.5.After 8 weeks of treatment,the expression levels of Nrf2,HO-1 and NQO1 in the sciatic nerve of the model group mice were significantly reduced compared with the control group(P <0.01).The HO-1 expression level of the mice in the low-dose group was higher than that in the model group(P <0.05).The expression levels of Nrf2,HO-1,NQO1 in the high-dose group and the ?-lipoic acid group were significantly higher than those in the model group(P <0.05).There was no statistical difference between the high-dose group and the alpha-lipoic acid group.Conclusions: Our results demonstrate that dioscin could ameliorate the behavioristics changes and improve pain threshold in PDPN mice by reducing oxidative stress.Nrf2/HO-1 signal pathway was involved in the neuroprotective effects.