南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (11): 1536-.

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胆碱与帕瑞昔布钠的协同镇痛作用及其机制

张娜，冯泽国，王汝欢，张卫东，余军，杜春彦，汪海   

  • 出版日期:2016-11-20 发布日期:2016-11-20

Synergistic analgesic effect of choline and parecoxib sodium in mice and the mechanism

  • Online:2016-11-20 Published:2016-11-20

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摘要： 目的探讨胆碱和帕瑞昔布钠在镇痛中的相互作用并对其机制进行初步研究。方法醋酸扭体模型：将150 只雄性昆 明小鼠随机分为4 组：（1）对照组（S）（n=10）：尾静脉注射0.9%的生理盐水0.2 mL/20 g；（2）胆碱组（C）（n=50）：50 只小鼠设立 5 个剂量即3、6、12、24、48 mg/kg；（3）特耐组（P）（n=50）：50 只小鼠设立5 个剂量即1.5、3、6、12、24 mg/kg；（4）联合用药组（C+ P）（n=40）：40 只小鼠设立4 个剂量，分别为两药ED50的1/2、1/4、1/8、1/16，进而可求出两药合用时的ED50。所有药物均在造 模前经尾静脉给予。胆碱给药时间为造模前2 h，帕瑞昔布钠为30 min。研究生理盐水对照组（S）、ED50胆碱组（C）、ED50帕 瑞昔布钠组（P）、以及1/2ED50胆碱和帕瑞昔布钠组[1/2（C+P）]对醋酸扭体模型小鼠血中细胞因子和炎症介质的影响。药物 预处理时间同上，在腹腔给予醋酸后10 min 立即实施摘眼球采血。所采血液采用ELISA 试剂盒检测IL-1、TNF-α、PGE2、 NF-kB、I-kB 的含量。结果（1）醋酸扭体模型中，胆碱和帕瑞昔布钠单独经尾静脉给药后所得的ED50，胆碱8.64 mg/kg，帕 瑞昔布钠6.33 mg/kg；二者联合用药时胆碱为2.13 mg/kg，帕瑞昔布钠为1.56 mg/kg；（2）在等辐射图见胆碱与帕瑞昔布钠合 用时的ED50实测值落在理论值的下方，两点作t 检验的P<0.05。联合用药指数CI<0.9；（3）与S 组比较，C组、P 组、1/2（C+P） 组中IL-1、TNF-α的含量均降低（P<0.05），且1/2（C+P）组比C组及P 组分别单独使用降低更加明显（P<0.05）；P 组以及1/2 （C+P）组中PGE2 含量较对照组均有降低（P<0.05），1/2（C+P）组与C 组相比PGE2 含量下降更多（P<0.05）；与S 组相比， NF-kB 的含量在C组、P 组、1/2（C+P）组中均降低（P<0.05），I-kB 的含量在1/2（C+P）组及C组中出现有统计学意义的降低， NF-kB、I-kB 在1/2（C+P）组中较P组有更明显降低（P<0.05）。结论胆碱与帕瑞昔布钠具有协同镇痛作用，二者的相互作用 可能与体内NF-kB的表达有关

Abstract: Objective To investigate the synergistic analgesic effect of choline and parecoxib sodium and study its mechanism. Methods In male Kunming mice with acetic acid-induced writhing, the ED50 of choline and parecoxib sodium (administered via the tail vein at 2 h and 30 min before modeling, respectively) and their combined use were determined. In saline (control) group, ED50 choline (C) group, ED50 parecoxib sodium (P) group, and 1/2ED50 choline and parecoxib sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min after intraperitoneal administration of acetic acid to detect the levels of IL-1, TNF-α, PGE2, NF-kB, and I-kB levels using ELISA kits. Results In the acetic acid-induced writhing model, the ED50 of choline and parecoxib sodium was 8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg, respectively. The isobolograms of parecoxib sodium and choline showed that the measured ED50 of the two drugs combined was below the theoretical ED50 value (P<0.05) with a combination index (CI) of <0.9. Compared with the control group, C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and TNF-α levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was significantly lower in P group and 1/2 (C+P) group compared with the control group (P<0.05). NF-κB and I-κB levels were significantly lowered in C, P, and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2 (C+P) group (P<0.05). Conclusion Choline and parecoxib sodium has a synergistic analgesic effect, and their interactions may involve the in vivo expression of NF-κB.