氟比洛芬酯对神经损伤大鼠疼痛治疗效果的研究

Investigation of flurbiprofen axetil on analgesic efficacy in nerve-injured rats

目的 研究不同剂量氟比洛芬酯（FA）对慢性压榨性损伤（CCI）模型大鼠神经行为学的影响.方法 成年SD大鼠30只按随机数字表法分成三组：对照组（C组）行假手术但不结扎神经;CCI组行坐骨神经慢性压迫性损伤,氟比洛芬酯治疗组（FA组）予CCI模型大鼠每12小时腹腔注射不同剂量的氟比洛芬酯（FA1组2 mg/kg、FA2组4 mg/kg、FA3组8 mg/kg、FA4组16 mg/kg）,每亚组均为5只大鼠,所有大鼠分别在术前及术后6 h、1 d、3 d、5 d、7 d测试热缩腿潜伏期（TWL）和机械性缩足反射阈值（MWT）.结果 CCI组和FA1-FA4组术后的TWL、MWT[TWL：（5.645±1.144）s、（5.901±0.914）s、（6.300±0.835）s、（7.631±0.597）s、（7.894±0.526）s;MWT：（5.14±0.71）g、（5.28±0.60）g、（6.74±0.50）g、（6.74±0.25）g、（6.70±0.42）g]均较C组[TWL：（12.396±1.144）s;MWT：（12.801±0.494）g]显著下降（TWL：t值：26.973、31.047、31.176、30.373、30.772;MWT：t值：44.192、48.132、51.136、54.326、46.937,均P〈0.05）,FA组随FA的剂量从2 mg/kg增大至16 mg/kg,TWL、MWT不断上升[TWL值：最小（5.030±0.240）s,最大（8.300±0.430）s;MWT值：最小（4.56±0.14）g,最大（7.11±0.20）g];与CCI组相比,FA1组的TWL和MWT与之差异无统计学意义（均P〉0.05）,FA2组、FA3组和FA4组的TWL和MWT明显升高[TWL：（6.300±0.835）s、（7.631±0.597）s、（7.894±0.526）s;MWT：（6.74±0.50）g、（6.74±0.25）g、（6.70±0.42）g]（TWL：t值分别为-3.768、-11.569、-13.867,MWT：t值分别为-3.898、-15.233、-14.801,均P〈0.05）;FA3组与FA4组的TWL和MWT差异均无统计学意义（均P〉0.05）.结论 4 mg/kg以上的氟比洛芬酯能明显减轻CCI模型大鼠的热痛敏和机械性痛敏症状,但有封顶效应,8 mg/kg时达到最大的镇痛效果.

Objective To investigate the influence of different doses of flurbiprofen axetil on neurological behavior in CCI rats.Methods All SD rats were randomly assigned to 3 groups：control group（C group）,operation but without CCI,n=5;CCI group,without injection,n=5;flurbiprofen axetil （FA） group,different doses of flurbiprofen axetil were intraperitoneally administered every 12 hours for 7 days beginning on postoperative 6 hours in CCI rats （FA1 group：2mg/kg,FA2 group：4mg/kg,FA3 group：8mg/kg,FA4 group：16mg/kg）,5 rats in each subgroup.The thermal withdrawal latency（TWL） and mechanical withdrawal threshold（MWT） were tested on preoperative 1,3,5 and 7 days and postoperative 1,3,5 and 7 days.Results Firstly,compared with C group[TWL：（12.396±1.144）s;MWT：（12.801±0.494）g],the TWL and MWT of CCI and FA groups[TWL：（5.645±1.144）s,（5.901±0.914）s,（6.300±0.835）s,（7.631±0.597）s,（7.894±0.526）s;MWT：（5.14±0.71）g,（5.28±0.60）g,（6.74±0.50）g,（6.74±0.25）g,（6.70±0.42）g]were significantly declined after surgery （tTWL=26.973,31.047,31.176,30.373,30.772;tMWT=44.192,48.132,51.136,54.326,46.937,all P〈0.05）,and the TWL and MWT of FA groups significantly improved with the doses from 2mg/kg to 16mg/kg of flurbiprofen axetil[TWL：the minimum （5.030±0.240）s,the maximum （8.300±0.430）s;MWT：the minimum （4.56±0.14）g,the maximum （7.11±0.20）g].Secondly,there were no statistically significant differences in TWL and MWT between CCI group and FA1 group（all P〉0.05）.However,the TWL and MWT of FA2 group,FA3 group and FA4 group[TWL：（6.300±0.835）s,（7.631±0.597）s,（7.894±0.526）s;MWT：（6.74±0.50）g,（6.74±0.25）g,（6.70±0.42）g] increased significantly compared with CCI group（tTWL=-3.768,-11.569,-13.867,tMWT=-3.898,-15.233,-14.801,all P〈0.05）.Thirdly,there were no statistically significant differences in TWL and MWT between FA3 group and FA4 group （all P〉0.05）.Conclusion Over 4mg/kg of flurbiprofen axetil can significantly reduce the thermal hyperalgesia and mechanical allodynia in CCI rats,however,there is a ceiling effect of flurbiprofen axetil,and the dosage of 8mg/kg can provide a maximum analgesic effect.