姜黄素对糖尿病神经病理性痛大鼠脊髓和背根神经节神经细胞凋亡的影响

目的 探讨姜黄素对糖尿病神经病理性痛(DNP)大鼠脊髓和背根神经节(DRG)神经细胞凋亡的影响.方法雄性SD大鼠108只,体重200～230 g,采用腹腔注射链唑霉素70 mg/kg的方法建立大鼠DNP模型.采用随机数字表法,将大鼠随机分为4组(n=27),正常对照组(C组):不制备DNP模型;DNP组;溶剂对照组(SC组)和姜黄素组(Cur组):于腹腔注射链唑霉素后14 d分别腹腔注射玉米油或姜黄素100 mg/kg(25 mg/ml),1次/d,连续2周.于链唑霉素给药前2 d、给药后14 d、姜黄素给药后3、7、14 d时测定机械缩足阈值(MWT)和热缩足潜伏期(TWL);于姜黄素给药后3、7、14 d时分别采用免疫组化法和Western blot法测定脊髓和DRG caspase-3和Bcl-2的表达水平,并测定神经细胞的凋亡率.结果 与C组比较,DNP组、SC组和Cur组MWT降低,TWL缩短,脊髓和DRG神经细胞凋亡率升高,caspase-3表达上调,Bcl-2表达下调(P＜0.05);与DNP组比较,Cur组MWT升高,TWL延长,脊髓和DBG神经细胞凋亡率降低,caspase-3表达下调,Bcl-2表达上调(P＜0.05),SC组差异无统计学意义(P＞0.05).结论 姜黄素可通过抑制脊髓和DRG神经细胞凋亡,从而减轻大鼠DNP,其机制与抑制caspase-3水平、增强Bcl-2水平有关.

Abstract：

Objective To investigate the effect of curcumin on the apoptosis in spinal cord and dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP) . Methods One hundred and eight male SD rats weighing 200-230 g were randomly divided into 4 groups ( n = 27 each): control group (group C), DNP group, solvent control group (group SC) and curcumin group (group Cur) . Diabetes was induced with intraperitoneal streptozocin 70 mg/kg. Successful induction of diabetes was defined as blood glucose ＞ 16.7 mmol/L. Curcumin and com oil 100 mg/kg (23 mg/ml) were given intraperitoneally once a day for 14 consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups respectively. Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before and 14 d after streptozocin injection and 3, 7 and 14 d after curcumin injection. The pain threshold measured at 14 d after administration of streptozocin decreased by more than 15% of the baseline in all the rats. The expression of caspase-3 and Bcl-2 in spinal cord and dorsal root ganglion was determined at 3, 7 and 14 d after curcumin injection by immuno-histochemistry and Western blot, and the neuronal apoptosis rate was determined by TUNEL. Results Compared with group C, MWT and Bcl-2 expression were significantly decreased, TWL was significantly shortened, the neurona lapoptosis rate and caspase-3 expression were significantly increased in DNP, SC and Cur groups ( P ＜ 0.05).Compared with group DNP, MWT and Bcl-2 expression were significantly increased, TWL was significantly prolonged, the neuronal apoptosis rate and caspase-3 expression were significantly decreased in Cur group ( P ＜0.05) . There was no significant difference in the parameters mentioned above between DNP and SC groups ( P ＞0.05). Conclusion Curcumin can attenuate DNP by inhibiting the apoptosis in spinal dorsal hom and dorsal root ganglion neurons in rats, and the inhibition of caspase-3 expression and increase in Bcl-2 expression are involved in the mechanism.

Effect of curcumin on apoptosis in spinal cord and dorsal root ganglion neurons in a rat model of diabetic neuropathic pain

Objective To investigate the effect of curcumin on the apoptosis in spinal cord and dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP) . Methods One hundred and eight male SD rats weighing 200-230 g were randomly divided into 4 groups ( n = 27 each): control group (group C), DNP group, solvent control group (group SC) and curcumin group (group Cur) . Diabetes was induced with intraperitoneal streptozocin 70 mg/kg. Successful induction of diabetes was defined as blood glucose ＞ 16.7 mmol/L. Curcumin and com oil 100 mg/kg (23 mg/ml) were given intraperitoneally once a day for 14 consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups respectively. Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before and 14 d after streptozocin injection and 3, 7 and 14 d after curcumin injection. The pain threshold measured at 14 d after administration of streptozocin decreased by more than 15% of the baseline in all the rats. The expression of caspase-3 and Bcl-2 in spinal cord and dorsal root ganglion was determined at 3, 7 and 14 d after curcumin injection by immuno-histochemistry and Western blot, and the neuronal apoptosis rate was determined by TUNEL. Results Compared with group C, MWT and Bcl-2 expression were significantly decreased, TWL was significantly shortened, the neurona lapoptosis rate and caspase-3 expression were significantly increased in DNP, SC and Cur groups ( P ＜ 0.05).Compared with group DNP, MWT and Bcl-2 expression were significantly increased, TWL was significantly prolonged, the neuronal apoptosis rate and caspase-3 expression were significantly decreased in Cur group ( P ＜0.05) . There was no significant difference in the parameters mentioned above between DNP and SC groups ( P ＞0.05). Conclusion Curcumin can attenuate DNP by inhibiting the apoptosis in spinal dorsal hom and dorsal root ganglion neurons in rats, and the inhibition of caspase-3 expression and increase in Bcl-2 expression are involved in the mechanism.