目的:探讨姜黄素对2型糖尿病诱导的神经病理性疼痛(DNP)大鼠机械痛敏(MWT)、热痛敏(TWL)、脊髓背角和背根神经节(DRG)的保护作用及机制.方法:高脂高糖饲料喂养8周诱导胰岛素抵抗后,继以单次小剂量链脲佐菌素(STZ)35 mg/kg腹腔注射,在注射STZ前和14 d后采用Electronic Von Fery触觉测痛仪和甩尾/足底测试仪测大鼠MWT和TWL,注射STZ 3 d后血糖≥16.7 mmol/L且在注射STZ 14 d后痛阈下降至基础值85%以下者入选为D组(81只).将D组随机分为3组(n=27):DNP组、DNP+姜黄素100 mg·kg-1·d-1组(DCur组)和DNP+溶剂组(DSC组),另取27只为正常对照组(C组),给予普通饲料喂养.给姜黄素3、7、14 d后测血糖、MWT与TWL,并在同时点取大鼠L4～L6脊髓和DRG,用免疫组化和免疫印迹法测定脊髓背角和DRG中免疫球蛋白重链结合蛋白(BiP)的表达.结果:与C组相比,DNP组各时点MWT降低,TWL缩短,血糖值升高,脊髓背角和DRG中BiP均出现表达上调(P<0.05).与DNP组相比,DCur组在给姜黄素7 d后MWT升高,TWL延长;给姜黄素14 d后脊髓背角和DRG中BiP表达下调(P<0.05).DSC组和DNP组相比差异无统计学意义.结论:BiP参与了2型糖尿病神经病理性疼痛的发病机制.姜黄素减轻2型糖尿病大鼠神经病理性疼痛的机制可能与抑制BiP表达有关.%AIM; To investigate the effects of immunoglobulin heavy chain - binding protein ( BiP) ,an endo-plasmic reticulum stress protein, on mechanical withdrawal threshold (MWT) , thermal withdrawal latency (TWL) , spinal dorsal horn and dorsal root ganglion ( DRG) in type II diabetic neuropathic pain rats treated with curcumin. METHODS: The rats were fed with a high - fat and high - fructose diet for 8 weeks to induce insulin resistance, and then were intraper-itoneally injected with streptozotocin (STZ, 35 mg/kg). Eighty -one rats were selected into experimental design as their blood glucose ≧16. 7 mmol/L 3 d after STZ injection and their MWT and TWL were decreased to 85% of the baseline val-ues 14 d after STZ injection. The rats were divided into 3 groups (n =27 each) : DNP group: type 2 diabetic neuropathic pain; DCur group: type 2 diabetic neuropathic pain and intraperitonal injection of curcumin at a dose of 100 mg·kg-1· d ; DSC group: type 2 diabetic neuropathic pain and intraperitonal injection of corn oil at a dose of 4 mL/kg. Another 27 normal SD male rats fed with normal forage were adopted as control group ( C group). MWT and TWL were measured at the time points of 3 d, 7 d and 14 d after curcumin injection. The lumbar segment 4～6 of the spinal cord and the correspond-ing DRG were removed at the same time. The expression of BiP was determined by immunohistochemical staining and West-ern blotting. RESULTS: Compared with C group, the rats in DNP group developed hyperglycemia and a decrease in MWT and TWL, as well as an increase in the activity of BiP in spinal dorsal horn and DRG (P <0. 05). Compared with DNP group, the rats in DCur group at the time point of 7 d significantly attenuated mechanical allodynia and thermal hyperalge-sia, and these effects were correlated with the inhibition of BiP hyper - activation at the time point of 14 d after treatmentrnwith curcumin ( P < 0. 05 ) . No significant difference of MWT, TWL and the expression of BiP between DNP group and SC group was observed. CONCLUSION: BiP participates in the pathogenesis of type II diabetic neuropathic pain. Curcumin attenuates the MWT and TWL in type 2 diabetic neuropathic pain rats. The mechanism may be involved in the inhibition of BiP expression by curcumin.
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