[Animal Modeling]-To study the synergistic analgesic effect and mechanism of choline and parecoxib sodium through mouse experiments

  Objective: To investigate the interaction between choline and parecoxib sodium in analgesia and to preliminarily explore its mechanism of action.

  Methods: Acetic acid writhing model: 150 male Kunming mice were randomly divided into 4 groups: (1) control group (S) (n=10): injection of 0.9? saline 0.2 mL/20 g into the tail vein; (2) gallbladder Alkaline group (C) (n=50): 50 mice were given 5 times, namely 3, 6, 12, 24, 48 mg/kg; (3)) Special resistance group (P) (n=50 ) ): 50 mice set 5 doses, namely 1.5, 3, 6, 12, 24 mg/kg; (4) concomitant drug group (C+P)) (N=40): 40 mice set 4 doses Dose, 2 doses per group When the ED50 is 1/2, 1/4, 1/8, 1/16, the ED50 of the combination of two drugs can be calculated. All drugs were administered through the tail vein before modeling. The choline administration time was 2 hours before modeling, and the palecoxib sodium administration time was 30 minutes. Saline control group (S), ED50 Colin group (C), ED50 Palecoxib sodium group (P) and 1/2 ED50 Colin and Palecoxib sodium group [1/2 (C + P)] Acetic acid writhing cytokines and inflammatory blood Model mice to study their effects on sex mediation. The pretreatment time of the drug was the same as above, and blood was collected from the eyeball 10 minutes after intraperitoneal injection of acetic acid. The collected blood was tested for IL-1, TNF-α, PGE2, NF-kB and I-kB levels using an ELISA kit.

  Results: (1) In the acetic acid writhing model, after only giving choline and palecoxib sodium from the tail vein, ED50, choline 8.64 mg/kg and palecoxib sodium 6.33 mg/kg were obtained; 2. When When the patient used choline and palecoxib sodium in combination, choline was 2.13 mg/kg and palecoxib sodium was 1.56 mg/kg. (2) In the contour map, the measured value of ED50 when choline is combined with parecoxib sodium is lower than the theoretical value. In the 2-point t test, u003c0.05, the combination index CIu003c0.9; (3) Compared with the S group, the C group, P group and 1/2 group (C+P) IL-1 and TNF-α levels reduce(). u003c0.05) and 1/2 (C+P) group were significantly lower than the C and P group when used alone (Pu003c0.05). The PGE2 content of P group and 1/2 (C+P) group was higher than that of control group (Pu003c0.05) and 1/2 (C+P) group. Decrease (Pu003c0.05)); NF-kB content in C, P, 1/2 (C+P) group (Pu003c0.05), 1 compared with S group, decreased by 2 (C+P) and group I -kB content C showed a statistically significant decrease, NF-kB, 1/2 (C+P) group I-kB was P, which was significantly lower than the group (Pu003c0.05).

  Conclusion: Choline and palecoxib sodium have a synergistic analgesic effect, and the interaction between the two may be related to the expression of NF-kB in the body