动物造模 z-bio 2022-04-01 469

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

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

　　Results: (1) In the acetic acid writhing model, the ED50 obtained after choline and parecoxib sodium were administered by tail vein alone, choline 8.64 mg/kg, parecoxib sodium 6.33 mg/kg; the two combined Choline was 2.13 mg/kg, and parecoxib sodium was 1.56 mg/kg; (2) in the isoradiogram, the measured ED50 value of choline and parecoxib sodium in combination was lower than the theoretical value, P<0.05 for two-point t-test. Combination medication index CI<0.9; (3) Compared with group S, the contents of IL-1 and TNF-α in group C, group P and 1/2 (C+P) group were all decreased (P<0.05), and 1 The /2 (C+P) group decreased more significantly than the C group and the P group respectively (P<0.05); the PGE2 content in the P group and the 1/2 (C+P) group was lower than that in the control group (P<0.05). Compared with group C, the content of PGE2 in 1/2 (C+P) group decreased more than that in group C (P<0.05); C+P) group were all decreased (P<0.05), and the content of I-kB was significantly decreased in 1/2 (C+P) group and C group. /2 (C+P) group had a more significant decrease than P group (P<0.05).

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