[Animal Experiment]-To study the synergistic analgesic effect of choline and parecoxib sodium and its mechanism

  Objective: To investigate the interaction between choline and parecoxib sodium in analgesia and to study its mechanism.

  Methods: Acetic acid writhing model: 150 male Kunming mice were randomly divided into 4 groups: (1) Control group (S) (n=10): 0.9% saline 0.2 mL/20 g was injected into the tail vein; (2) ) Choline group (C) (n=50): 50 mice set up 5 doses, namely 3, 6, 12, 24, 48 mg/kg; (3) Special resistance group (P) (n=50): 50 mice set up 5 doses, namely 1.5, 3, 6, 12, 24 mg/kg; (4) Combination group (C+P) (n=40): 40 mice set up 4 doses, two respectively The ED50 of the medicine is 1/2, 1/4, 1/8, 1/16, and the ED50 of the two medicines can be calculated. All drugs were given via the tail vein before modeling. Choline administration time was 2 hours before modeling, and parecoxib sodium was 30 minutes. Study the normal saline control group (S), ED50 choline group (C), ED50 parecoxib sodium group (P), and 1/2 ED50 choline and parecoxib sodium group [1/2 (C+P) ] Effect on cytokines and inflammatory mediators in the blood of acetic acid writhing model mice. The pretreatment time of the drug was the same as above, and the eyeball was taken immediately after 10 minutes of intraperitoneal administration of acetic acid. The collected blood was tested for the levels of IL-1, TNF-α, PGE2, NF-kB, and I-kB using an ELISA kit.

  Results: (1) In the acetic acid writhing model, the ED50 of choline and parecoxib sodium after the tail vein administration alone was 8.64 mg/kg choline and 6.33 mg/kg parecoxib sodium; the two were combined Choline was 2.13 mg/kg and parecoxib sodium was 1.56 mg/kg during medication; (2) In the isoradiogram, the measured ED50 value of choline and parecoxib sodium when used in combination fell below the theoretical value. P<0.05 for the two-point t test. Combination index CI<0.9; (3) Compared with group S, the levels of IL-1 and TNF-α in group C, group P, and 1/2 (C+P) group all decreased (P<0.05), and 1 /2 (C+P) group reduced more significantly than the C and P groups when used alone (P<0.05); PGE2 content in the P group and 1/2 (C+P) group was lower than the control group (P< 0.05), the content of PGE2 in group 1/2 (C+P) decreased more than group C (P<0.05); compared with group S, the content of NF-kB in group C, P, 1/2 ( C+P) group decreased (P<0.05), the content of I-kB in 1/2 (C+P) group and group C showed a statistically significant decrease, NF-kB, I-kB were at 1 /2 (C+P) group had a more significant decrease than P group (P<0.05).

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