姜黄素对2型糖尿病大鼠神经病理性痛及脊髓背角和背根神经节IRE1α表达的影响
Effects of curcumin on type 2 diabetic neuropathic pain and expression of inositol-requiring enzyme 1α in spinal dorsal horn and dorsal root ganglia in rats
摘要目的 评价姜黄素对2型糖尿病大鼠神经病理性痛及脊髓背角和背根神经节肌醇需求激酶1α(IRE1α)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 14 d后机械缩足阈值(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,将其随机分为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 14 d后腹腔注射姜黄素或玉米油100 mg/kg(25mg/ml),1次/d,连续14d,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天时测定MWT和TWL,痛阈测定后用Western blot法检测大鼠脊髓背角和背根神经节IREIα的表达.结果 与C组比较、DNP组、Cur组和SC组MWT降低,TWL缩短,脊髓背角和背根神经节IRE1α表达上H调(P<0.05);与DNP组比较,Cur组MWT升高,TWL延长,脊髓背角和背根神经节IREIα表达下调(p<0.05).SC组和DNP组上述指标比较差异无统计学意义(P>0.05).结论 姜黄素可减轻2型糖尿病大鼠神经病理性痛,其机制与抑制脊髓背角和背根神经节IRE1α表达有关.
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abstractsObjective To investigate the effects of curcumin on type 2 diabetic neuropathic pain (DNP)and expression of inositol-requiring enzyme 1α (IRE1α) in spinal dorsal horn and dorsal root ganglia (DRG) in rats.Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin (STZ) 35 mg/kg,and confirmed by fasting blood glucose level > 16.7 mmol/L in male SD rats.Type 2 DNP was confirmed by the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWI.) measured on day 14 after STZ administration < 80% of the baseline value.The rats were then randomly divided into 3 groups ( n =27 each):DNP group,curcumin group (group Cur) and solvent control group (group SC).Curcumin and corn oil 100 mg/kg (25 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.Another 27 rats were chosen and served as control group (group C) and fed with common fodders.MWT and TWL were measured at 3,7 and 14 day after curcumin administration.The expression of IRE1α in spinal dorsal horn and DRG was detected by Western blot.Results Compared with group C,MWT was significantly decreased and TWL was significantly shortened,and the expression of IRE1α was up-regulated in DNP,Cur,and SC groups (P < 0,05),Compared with group DNP,MWT were significantly increased,TWL was significantly prolonged,and the expression of IRE1α in spinal dorsal horn and DRG was down-regulated in group Cur (P < 0.05).There was no significantdifference in the parameters mentioned above between DNP and SC groups (P > 0.05).Conclusion Curcumin can attenuate type 2 1)NP and inhibition of the expression of IRE1α in spinal dorsal horn and DRG is involved in the mechanism.
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