CAJ | 학술논문

目的评价姜黄素对2型糖尿病神经病理性痛大鼠脊髓背角及背根神经节磷酸化细胞外信号调节激酶(p-ERK)、磷酸化环磷酸腺苷反应元件结合蛋白(p-CREB)表达的影响.方法高脂高糖喂养雄性SD大鼠8周诱导胰岛素抵抗,以35 mg/kg链脲佐菌素(STZ)单次腹腔注射,3d后血糖≥16.7 mmol/L大鼠为2型糖尿病大鼠.注射STZ后14d机械缩足阈(MWT)和热缩足潜伏期(TWL)低于基础值80％的大鼠为2型糖尿病神经病理性痛大鼠,采用随机数字表法,将其分为3组(n=27):2型糖尿病神经病理性痛组(DNP组)、姜黄素组(Cur组)和溶剂对照组(SC组).Cur组和SC组于注射STZ后14 d腹腔注射姜黄素和玉米油100 mg/kg(25 mg/ml),1次/d,连续14 d,DNP组不做任何处理.另取27只正常大鼠为对照组(C组),给予普通饲料喂养.给予姜黄素后第3、7和14天(T13)时测定MWT和TWL后各组随机取9只大鼠处死,取L4-6脊髓背角和背根神经节,采用Westem blot法检测p-ERK和p-CREB的表达.结果与C组比较,DNP组和SC组T13时MWT降低,TWL缩短,脊髓背角和背根神经节p-ERK、p-CREB表达上调,Cur组T1时MWT降低,TWL缩短,脊髓背角和背根神经节p-ERK、p-CREB表达上调(P＜0.05)；与DNP组比较,Cur组T23时MWT升高,TWL延长,脊髓背角和背根神经节p-ERK、p-CREB表达下调(P＜0.05).DNP组与SC组各指标比较差异无统计学意义(P＞0.05).结论姜黄素可通过抑制脊髓背角和背根神经节p-ERK、p-CREB表达上调减轻大鼠2型糖尿病神经病理性痛.
목적 평개강황소대2형당뇨병신경병이성통대서척수배각급배근신경절린산화세포외신호조절격매(p-ERK)、린산화배린산선감반응원건결합단백(p-CREB)표체적영향.방법 고지고당위양웅성SD대서8주유도이도소저항,이35 mg/kg련뇨좌균소(STZ)단차복강주사,3d후혈당≥16.7 mmol/L대서위2형당뇨병대서.주사STZ후14d궤계축족역(MWT)화열축족잠복기(TWL)저우기출치80％적대서위2형당뇨병신경병이성통대서,채용수궤수자표법,장기분위3조(n=27):2형당뇨병신경병이성통조(DNP조)、강황소조(Cur조)화용제대조조(SC조).Cur조화SC조우주사STZ후14 d복강주사강황소화옥미유100 mg/kg(25 mg/ml),1차/d,련속14 d,DNP조불주임하처리.령취27지정상대서위대조조(C조),급여보통사료위양.급여강황소후제3、7화14천(T13)시측정MWT화TWL후각조수궤취9지대서처사,취L4-6척수배각화배근신경절,채용Westem blot법검측p-ERK화p-CREB적표체.결과 여C조비교,DNP조화SC조T13시MWT강저,TWL축단,척수배각화배근신경절p-ERK、p-CREB표체상조,Cur조T1시MWT강저,TWL축단,척수배각화배근신경절p-ERK、p-CREB표체상조(P＜0.05)；여DNP조비교,Cur조T23시MWT승고,TWL연장,척수배각화배근신경절p-ERK、p-CREB표체하조(P＜0.05).DNP조여SC조각지표비교차이무통계학의의(P＞0.05).결론 강황소가통과억제척수배각화배근신경절p-ERK、p-CREB표체상조감경대서2형당뇨병신경병이성통.
Objective To evaluate the effects of curcumin on the expression of phosphorylated extracellular signal-related kinase (p-ERK) and phosphorylated cAMP response element binding protein (p-CREB) in the spinal dorsal horn and dorsal root ganglion (DRG) in type 2 diabetic neuropathic pain (DNP) in rats.Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin (STZ) 35mg/kg,and confirmed by fasting blood glucose level≥ 16.7 mmol/L in male Sprague-Dawley rats.Type 2 DNP was confirmed by the mechanical withdrawal threshold (MWT) and thermal withdraw latency (TWL) measured on day 14 after STZ administration ＜ 80％ of the baseline value,and the rats with type 2 DNP were randomly divided into 3 groups (n =27 each):type 2 DNP group (group DNP),curcumin group (group Cur) and solvent control group (group SC).Curcumin and corn oil 100 mg/kg (25 mg/ml) were injected intraperitoneally once a day for 14consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups,respectively.Another 27 normal rats were served as control group (group C) and were fed with common forage.MWT and TWL were measured at 3,7 and 14 days after curcumin injection (T1 3),and the lumbar segment 4-6 of the spinal cord and DRGs were removed at the same time for determination of the expression of p-ERK and p-CREB (by Western blot).Results Compared with group C,MWT was significantly decreased,TWL was shortened,and the expression of p-ERK and p-CREB in spinal dorsal horn and DRGs was up-regulated at T1-3 in DNP and SC groups,and at T1 in Cur group (P ＜ 0.05).Compared with group DNP,MWT was significantly increased,TWL was prolonged,and the expression of p-ERK and p-CREB in spinal dorsal horn and DRGs was down-regulated at T2,3 in Cur group (P ＜0.05).There was no significant difference in the MWT,TWL and expression of p-ERK and p-CREB between DNP and SC groups (P ＞ 0.05).Conclusion Curcumin can attenuate type 2 diabetic DNP by inhibiting up-regulation of the expression of p-ERK and p-CREB in the spinal dorsal horn and DRG in rats.