The Role Of G6PD Deficiency In Diabetic Neuropathic Pain

Background:Diabetic neuropathy is one of the most common and the most disabling of diabetes mellitus chronic complications.The pathogenesis of diabetic peripheral neuropathy(DPN)is complex,and oxidative stress is thought to be an important pathway.G6 PD is one of the important reductasein vivo,and plays an important role in the occurrence and development of diabetes and its complications.Objective:To observe the effect of intraperitoneal injection of Kallikrein(Pancreatic,PKK)on peripheral neuropathy in type 1 diabetic mice.Moreover,to investigate the role of glucose-6-phosphate dehydrogenase(G6PD)in diabetic neuropathic painin STZ induced diabetic rats.Methods:Akita mice were selected as type 1 diabetes mellitus(DM).Intraperitoneal injection of streptozotocin(STZ,70mg/kg)induced type 1 diabetic modelin adult female rats.The blood glucose and body weight were measured every week.The ultrastructure of DRG neurons were observed by transmission electron microscopy(TEM).The expression of G6 PD in mRNA level and in protein level were measured by real time quantitative PCR and Western blot analysis.Mechanical withdrawal threshold(paw withdrawal threshold,PWT)of rats were measured by using von Frey(0.4g-15.0g)filaments.And thermal withdrawal latency(paw withdrawal latency,PWL)were determined by heat radiation method.Results:(1)The blood glucose of NS group was significantly increased compared with the WT group.And the body weight of NS group was markedly lower than WT group.There was no significant difference in blood glucose or body weight between NS group and PKK group.(2)Compared with WT group,transmission electron microscope images appeared mitochondrial swelling,increased microvascular microvilli and disorganized microtubule structure in NS group.The pathological changes of PKK group had different degrees of improvement.(3)The gene expression of G6 PD in NS group was significantly lower compared with WT group,and the level of G6 PD was significantly increased after PKK treatment.(4)According to PWT and PWL of rats,we found that mechanical allodynia and thermal hyperalgesia was induced 2 weeks after STZ injection and lasted for 2 weeks.STZ injection also led to a marked downregulation expression of G6 PD compared with age-matched control rats.In addition,intrathecal injection of overexpression adenoviral of G6 PD upregulated the expression of G6 PDand alleviate limb hyperalgesia.Conclusion:In the diabetic animal models,the expression of G6 PD are decreased in the DRGs which is associated with neuropathic pain.PKK treatment can improve the ultrastructural lesions in diabetes significantly and upregulate the expression of G6PD.