Effects of curcumin on expression of receptor for advanced glycation end-products in spinal dorsal horn and dorsal root ganglion of rats with type 2 diabetic neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of curcumin on the expression of receptor for advanced glycation end-products (RAGE) in the spinal dorsal horn and dorsal root ganglion (DRG) of the rats with type 2 diabetic neuropathic pain (DNP).Methods Male Sprague-Dawley rats,weighing 160-180 g,were used in this study.Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet for 8 weeks and intraperitoneal streptozotocin (STZ) 35 mg/kg and confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later.Type 2 DNPwas confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after STZ administration less than 80％ of the baseline value.Eighty-one rats with type 2 DNP were randomly divided into 3 groups (n =27 each) using a random number tableDNP group,DNP + curcumin group (DCur group),and DNP+ solvent group (group DSC).In DCur and DSC groups,curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml · kg-1 · d-1 were injected intraperitonally,respectively,for 14 consecutive days starting from the day 14 after STZ administration.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before STZ injection,at day 14 after STZ injection,and on 3,7 and 14 days after curcumin injection.RAGE positive cells were determined by immuno-histochemistry and the expression of RAGE by Western blot in the spinal dorsal horn and DRG after MWT and TWL were measured on 3,7 and 14 days after curcumin injection.Results Compared with group C,MWT was significantly decreased and TWL was shortened at 14 days after STZ injection and each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was increased at each time point after curcumin injection,and the expression of RAGE was up-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DNP.Compared with group DNP,MWT was significantly increased and TWL was prolonged at each time point after curcumin injection,the rate of RAGE positive cells in the spinal dorsal horn and DRG was significantly decreased at 7 and 14 days after curcumin injection,and the expression of RAGE was down-regulated in the spinal dorsal horn at each time point after curcumin injection and in the DRG at 7 and 14 days after curcumin injection in group DCur,and no significant change was found in the parameters mentioned above in group DSC.Conclusion The mechanism by which curcumin attenuates DNP may be related to inhibition of up-regulated expression of RAGE in the spinal dorsal horn and DRG of rats with type 2 diabetes mellitus.