|
摘要：
目的 观察不同剂量TAK-242（瑞沙托维）对大鼠糖尿病周围神经痛（diabetic peripheral neuropathy, DPN）的镇痛效果，探讨高迁移率族蛋白1（high mobility group box-1 protein, HMGB1）-Toll样受体4（Toll-like receptors 4, TLR4）（HMGB1-TLR4）轴在DPN致病过程中的作用。 方法 链脲佐菌素（streptozotocin, STZ） 腹腔注射法制备DPN大鼠模型，采用随机数字表法分为模型组（DPN大鼠模型）、低剂量组（TAK-242，1 mg/kg）、中剂量组（TAK-242，3 mg/kg）、高剂量组（TAK-242，10 mg/kg）和曲马多组（曲马多，20 mg/kg），每组10只。设立空白对照组（10只）。在造模前1 d（B1）及造模后第7、14天（A7、A14），对大鼠进行行为学分析以及刺激试验，比较热辐射刺激下后肢抬足潜伏期、冷刺激下大鼠足趾缩足反射潜伏期（plantar withdrawal latency, PWL）以及机械性触觉异位性疼痛阈值的变化。采用ELISA法检测各组大鼠外周血中IL-12、IL-6水平。 结果 模型组大鼠热辐射下后肢抬足潜伏期、冷刺激下PWL以及机械性触觉异位性疼痛阈值均较空白对照组下降 （P<0.05）。中剂量及高剂量TAK-242干预后，各刺激试验的潜伏期及疼痛阈值均较模型组、低剂量组升高（P<0.05）。 ELISA检测显示中剂量及高剂量TAK-242治疗后，促炎因子IL-12及IL-6表达量较模型组、低剂量组、曲马多组下降（P<0.05）。 结论 中剂量及高剂量TAK-242可提高DPN大鼠的疼痛阈值，在减少促炎因子（IL-12、IL-6）的表达量方面优于传统药物曲马多。TAK-242可能是治疗大鼠DPN的有效药物。
|
|
Abstract: Ｏｂｊｅｃｔｉｖｅ To examine the effect of TAK-242, a blocker for high mobility group box-1 protein-Toll-like receptors 4 (HMGB1-TLR4) pathway, on diabetic peripheral neuropathic pain (DPN) rat models. Methods Sixty SD rats were randomly divided into control group (n=10), model group (n=10), low dose group (TAK-242, 1 mg/kg, n=10), middle dose group (TAK-242, 3 mg/kg, n=10), high dose group (TAK-242, 10 mg/kg, n=10) and tramadol group (tramadol, 20 mg/kg, n=10). Heat radiation test, cold plate test and von Frey filament test were performed to examine pain threshold for heat, cold and mechanical stimulation. These tests were conducted one day before experiment (B1) and 7 (A7) and 14 (A14) days after the establishment of DPN models. The levels of proinflammatory cytokines (IL-12, IL-6) in plasma were measured with ELISA assay. Results DPN rats displayed lower pain threshold to heat, cold and mechanical stimulation than control rats (P<0.05). TAK-242 at both middle and high doses significantly increased the pain threshold, relative to the model group and low-dose group (P<0.05). The elevated levels of proinflammatory cytokines (IL-12 and IL-6) in DPN rats were reversed by middle and high doses of TAK-242 (P<0.05). Conclusions TAK-242 (3-10 mg/kg) could relieve pain symptoms probably via decreasing the levels of pro-inflammatory cytokines (IL-12, IL-6) in DPN rats, and may be a safe and effective drug for the treatment of hyperalgesia in DPN.
|
