CAJ | 학술논문

目的评价姜黄素对糖尿病神经病理性痛(DNP)大鼠脊髓背角NR2B与NR1活性的影响.方法高糖高脂饲料喂养SD大鼠8周诱导胰岛素抵抗,继以单次小剂量链脲佐菌素(STZ)35 mg/kg腹腔注射,3d后血糖≥16.7 mmol/L为糖尿病大鼠;14 d后测定机械缩足反应阈(MWT)和热缩足反应潜伏期(TWL),低于基础值80％的大鼠为DNP大鼠,采用随机数字表法分为3组(n=27):DNP组、DNP+姜黄素组(DCur组)和DNP+溶剂组(DSC组).DCur组和DSC组于注射STZ 14 d后分别腹腔注射姜黄素100 mg·kg-1·d-1和玉米油4 ml·kg-1 ·d-1,连续注射14 d.另取27只正常大鼠为对照组(C组).给予姜黄素3、7和14 d后测定MWT和TWL,并在同时点取大鼠L4-6脊髓,用免疫组化和免疫印迹法测定脊髓背角pTyr1472-NR2B与pSer896-NR1的表达.结果与C组比较,DNP组各时点MWT降低,TWL缩短,脊髓背角pTyr1472-NR2B表达上调(P＜0.05);与DNP组比较,DCur组给予姜黄素7d后MWT升高,TWL延长,给予姜黄素3d后脊髓背角pTyr1472-NR2B表达下调(P＜0.05);DSC组与DNP组各指标比较差异无统计学意义(P＞0.05);4组脊髓背角pSer896-NR1表达差异无统计学意义(P＞0.05).结论姜黄素减轻大鼠DNP的机制可能与抑制脊髓背角NR2B激活有关,而与脊髓背角NR1无关.
목적 평개강황소대당뇨병신경병이성통(DNP)대서척수배각NR2B여NR1활성적영향.방법 고당고지사료위양SD대서8주유도이도소저항,계이단차소제량련뇨좌균소(STZ)35 mg/kg복강주사,3d후혈당≥16.7 mmol/L위당뇨병대서;14 d후측정궤계축족반응역(MWT)화열축족반응잠복기(TWL),저우기출치80％적대서위DNP대서,채용수궤수자표법분위3조(n=27):DNP조、DNP+강황소조(DCur조)화DNP+용제조(DSC조).DCur조화DSC조우주사STZ 14 d후분별복강주사강황소100 mg·kg-1·d-1화옥미유4 ml·kg-1 ·d-1,련속주사14 d.령취27지정상대서위대조조(C조).급여강황소3、7화14 d후측정MWT화TWL,병재동시점취대서L4-6척수,용면역조화화면역인적법측정척수배각pTyr1472-NR2B여pSer896-NR1적표체.결과 여C조비교,DNP조각시점MWT강저,TWL축단,척수배각pTyr1472-NR2B표체상조(P＜0.05);여DNP조비교,DCur조급여강황소7d후MWT승고,TWL연장,급여강황소3d후척수배각pTyr1472-NR2B표체하조(P＜0.05);DSC조여DNP조각지표비교차이무통계학의의(P＞0.05);4조척수배각pSer896-NR1표체차이무통계학의의(P＞0.05).결론 강황소감경대서DNP적궤제가능여억제척수배각NR2B격활유관,이여척수배각NR1무관.
Objective To evaluate the effects of curcumin on the activity of NR2B and NR1 in the spinal dorsal horn in a rat model of diabetic neuropathic pain (DNP).Methods Diabetes mellitus was induced by high-sucrose and high-fat diet and intraperitoneal streptozotocin 35 mg/kg,then confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later in male Sprague-Dawley rats.DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after streptozotocin administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups (n =27 each) using a random number table:DNP,DNP+ curcumin group (group DCur)and DNP + solvent control group (group DSC).Curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml· kg-1 · d-1 were injected intraperitoneally for 14 consecutive days starting from 14 days after administration of streptozotocin in DCur and DSC groups,respectively.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.At 3,7 and 14 days after curcumin injection,MWT and TWL were measured and the lumbar segments (L4-6) of the spinal cord were removed.The expression of pTyr1472-NR2B and pSer896-NR1 in the spinal dorsal horn was determined by immunohistochemistry and Western blot.Results Compared with group C,MWT was significantly decreased,TWL was shortened,and the expression of pTyr1472-NR2B was up-regulated at each time point in group DNP.Compared with group DNP,MWT was significantly increased,and TWL was prolonged at 7 days after curcumin injection,and the expression of pTyr1472-NR2B was down-regulated at 3 days after curcumin injection in group DCur.There was no significant difference in each parameter between DNP and DSC groups,and in the expression of pSer896-NR1 between the four groups.Conclusion The mechanism by which curcumin mitigates neuropathic pain in type 2 diabetic rats may be related to inhibition of up-regulation of pTyr1472-NR2B expression,while unrelated to pSer896-NR1 expression in the spinal dorsal horn.