芬太尼联合纳洛酮对大鼠疼痛模型镇痛效果及相关机制研究

Analgesic effect and related mechanism of fentanyl combined with naloxone on rat pain model

目的分析芬太尼联合纳洛酮对大鼠疼痛模型镇痛效果及相关机制研究。方法将40只大鼠随机数字表法分成5组:生理盐水组(NS组)、疼痛模型组(CCI组)、芬太尼组(FN组)、纳洛酮组(NL组)、芬太尼+纳洛酮组(FN+NL组),每组8只。通过结扎坐骨神经制备大鼠坐骨神经慢性压迫(CCI)模型。FN组腹腔注射0.5μg/kg芬太尼,NL组腹腔注射10 ng/kg纳洛酮,FN+NL组腹腔注射0.5μg/kg芬太尼+10 ng/kg纳洛酮,1次/d,连续给药7 d。NS组和CCI组给予等体积生理盐水。于规定时间对大鼠体重、机械缩足反应阈值(MWT)、热缩足反应潜伏期(TWL)、内源性阿片样物质、炎性因子、黏附分子CD11b/c、胶质原纤维酸性蛋白(GFAP)的含量进行检测。结果与NS组相比,CCI组给药1、3、7 d后大鼠体重、MWT、TWL均显著降低,术后给药30 min、6 h和24 h后的内啡肽(β-EP)、强啡肽(DynA1-13)、亮氨酸脑啡肽(L-EK)以及肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、CD11b/c和GFAP表达量均显著升高,差异均有统计学意义(P<0.05)。与CCI组相比,FN组、NL组、FN+NL组大鼠体重、MWT、TWL均显著升高,β-EP、TNF-α、IL-6、IL-1β、IL-10、CD11b/c和GFAP表达量均显著降低,DynA1-13、L-EK显著升高,差异均有统计学意义(P<0.05)。与FN组、NL组相比,FN+NL组大鼠体重、MWT、TWL均显著升高,β-EP、TNF-α、IL-6、IL-1β、IL-10、CD11b/c和GFAP表达量均显著降低,DynA1-13、L-EK显著升高,差异均有统计学意义(P<0.05)。结论纳洛酮能够增强芬太尼的镇痛效果,其机制可能是纳洛酮与芬太尼联合使用,上调了大鼠体内IL-10、内源性阿片样物质的表达,下调了其他炎性因子及CD11b/c、GFAP的表达。

Objective To analyze the analgesic effect and related mechanism of fentanyl combined with naloxone on rat pain model.Methods Forty rats were divided into 5 groups by random number table:normal saline group(NS group),pain model group(CCI group),fentanyl group(FN group),naloxone group(NL group),fentanyl+naloxone group(FN+NL group),8 rats in each group.The chronic compression of sciatic nerve(CCI)was established by ligation of sciatic nerve.Fentanyl 0.5μg/kg was intraperitoneally injected into FN group,naloxone 10 ng/kg was intraperitoneally injected into NL group,and fentanyl(0.5μg/kg)and naloxone 10 ng/kg were intraperitoneally injected into FN+NL group,once a day for 7 days.NS group and CCI group were given equal volume of normal saline.The body weight,mechanical withdrawal threshold(MWT),thermal withdrawal latency(TWL),endogenous opioids,inflammatory factors,adhesion molecule CD11b/c and glial fibrillary acidic protein(GFAP)were measured at the specified time.Results Compared with NS group,the body weight,MWT and TWL of rats in CCI group decreased significantly after 1,3,and 7 days administration,and the expression of endorphins(β-EP),dynorphin(DynA1-13),leucine enkephalin(L-EK)30 min,6 h and 24 h after administration,tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-10(IL-10),CD11b/c and GFAP increased significantly(P<0.05).Compared with CCI group,the body weight,MWT and TWL of rats in FN group,NL group and FN+NL group were significantly higher,the expression ofβ-EP,TNF-α,IL-6,IL-1β,IL-10,CD11b/c and GFAP were significantly lower,DynA1-13 and L-EK were significantly higher,the difference was statistically significant(P<0.05).Compared with FN group,NL group,the body weight,MWT and TWL of rats in FN+NL group were significantly higher,the expression ofβ-EP,TNF-α,IL-6,IL-1β,IL-10,CD11b/c and GFAP were significantly lower,DynA1-13 and L-EK were significantly higher,the difference was statistically significant(P<0.05).Conclusion Naloxone can enhance the analgesic effect of fentanyl.The mechanism may be that naloxone combined with fentanyl can up regulate the expression of IL-10,endogenous opioid substances,down regulate the expression of other inflammatory factors and CD11b/c,GFAP.