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Objective To evaluate the changes in the expression of acetylated histone 3 lysine 9 (H3K9Ac) and methyl-CpG-binding protein 2 (MeCP2) in the spinal cord and dorsal root ganglion (DRG) of rats with diabetic neuropathic pain (DNP).Methods Pathogen-free male Sprague-Dawley rats,weighing 120-160 g,were fed a high-fat and high-sucrose diet for 8 weeks,then streptozocin 35 mg/kg was intraperitoneally injected,and type 2 diabetes mellitus was confirmed by blood glucose level ≥ 16.7 mmol/L 3 days later.DNP model was considered successful when the decrease in pain threshold ＜ 85％ of the baseline value on 14 days after injection,otherwise it was considered as non-DNP (NDNP).Eighteen rats with DNP and NDNP served as DNP and NDNP groups,respectively,and another 18 normal rats served as control group (group C).At 3,7 and 14 days after successful establishment of the model,the mechanical paw withdrawal threshold and thermal paw withdrawal latency were measured in group DNP and at the corresponding time points in C and NDNP groups,and then rats were sacrificed,and the lumbar segment of the spinal cord and DRGs were removed for determination of the expression of H3K9Ac and MeCP2 by Western blot.Results Compared with C and NDNP groups,mechanical paw withdrawal threshold was significantly decreased,thermal paw withdrawal latency was shortened,the expression of H3K9Ac in the spinal cord and DRGs was up-regulated,and the expression of MeCP2 in the spinal cord and DRGs was down-regulated at 3,7 and 14 days after successful establishment of the model in group DNP (P＜0.05).Conclusion The maintenance mechanism of DNP may be related to up-regulated expression of H3K9Ac and down-regulated expression of MeCP2 in rats with DNP.
RESUMEN
AIM:ToexplorewhetherMCP-1-JAK2/STAT3signaltransductioninthespinaldorsalhornin-volves the formation and development of rat type 2 diabetic neuropathic pain (DNP).METHODS: The male Sprague-Dawley rats were fed with a high-fat and fructose diet for 8 weeks,and then received a single intraperitoneal streptozocin in-jection to prepare the type 2 DNP model.The type 2 DNP rats were randomly divided into 4 groups (n=16):DNP group, MCP-1 neutralizing (DM) group, DNP+AG490 (DA) group and solvent control (SC) group.A catheter of PE-10 was placed into the subarachnoid space of the rats in groups DM , DA and SC.After 3 d, the rats in DM,DA and SC groups were injected with MCP-1 inhibitor 10μL at 0.1 mg/L, AG490 10μL at 1 mmol/L and DMSO 10μL at 3.5%once a day for 14 days, respectively.Another 16 normal rats were selected as control (C) group and were fed with common forage. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1, 3, 7 and 14 d after subarachnoid injection .The lumbar segments 4-6 of the spinal cord were removed at the same time for determination of the expressions of p-JAK2 and p-STAT3 by Western blot .RESULTS:Compared with C group , MWT was significantly de-creased, TWL was shortened and the expression of p-JAK2 and p-STAT3 in the spinal dorsal horn was up-regulated at 1, 3, 7 and 14 d in DNP and SC groups (P0.05).CONCLUSION:The MCP-1-JAK2/STAT3 signal transduction in the spinal dorsal horn involves the formation and development of DNP in rats .