[Animal Modeling]-To study the synergistic analgesic effect of choline and parecoxib sodium and its mechanism 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 Kunming male mice were randomly divided into 4 groups: (1) Control group (S) (n = 10): 0.9% normal saline 0.2 mL/20 g was injected into the tail vein; (2) Choline group (C) (n = 50): 5 doses of 50 mice, namely 3, 6, 12, 24, 48 mg/kg; (3) special resistance group (3) 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 ED50 4 doses, 2 doses per dose is calculated as two 1/2, 1/4, 1/8, 1/16 and ED50 of a mouse. Before modeling, all drugs were administered via the tail vein. The administration time of choline was 2 hours before modeling, and the time of parosib sodium was 30 minutes. In the saline control group (S), ED50 choline group (C), ED50 parosibu sodium group (P) and 1/2 ED50 choline and parosibu sodium group [1/2(C + P )] Inflammatory mediators in model mice distorted by blood cytokines and acetate. The pretreatment time of the drug is the same as above, and the eyeballs are collected 10 minutes after intraperitoneal administration of acetic acid. The collected blood was tested for 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 tail vein administration was 8.64 mg/kg choline and 6.33 mg/kg parecoxib sodium; 2. Combined with the patient When used, choline was 2.13 mg/kg and parecoxib sodium was 1.56 mg/kg; (2) the radiograph combined with choline and cocoxib sodium, the measured ED50 of this case was lower than the theoretical value. Next, P\u003c0.05 performs a 2-point t test. Combination index CI\u003c0.9; (3) Compared with group S, the levels of IL-1 and TNF-α in group C, group P and 1/2 (C + P) all decreased (P). (U003c0.05), the 1/2 (C + P) group was significantly lower than the C and P groups (P\u003c0.05); the PGE2 content of the P and 1/2 (C + P) groups was lower than the control group (P\u003c0.05), the content of PGE2 in the 1/2 (C + P) group was lower than that in the C group (P\u003c0. 05); compared with the S group, C, P, 1/2 (C + P) group ( P\u003c0.05), 1/2 (C + P) group NF-kB content decreased; I-kB content reduction in group I and C group is statistically significant, compared with P group, 1/2 (C + P) The group NF-kB and I-kB decreased significantly (P\u003c0.05).

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