ABSTRACT

Objective: To explore the application methods of MAPK signal pathway inhibitor SP600125 and SB203580’s long-term experiments in vivo.

Methods: Fifty-five healthy New Zealand rabbits were randomly divided into blank control group, model control group, SP/SB low dose group, SP/SB high dose group, SP/SB blank group, DMSO control group, DMSO blank group and positive control group. Since the first day of the experiment each group was administrated the corresponding treatment for four weeks continuously, then the myocardial JNK and the total protein of p38, protein phosphorylation and its gene expression levels were also detected.

Results: After treated with Adriamycin (i.v.), the myocardial (phosphoryalate-JNK) p - JNK and p-p38 levels in all groups were increased to varying degrees, of which the model control group raised the most significant (p < 0.05). Compared with model control group, the myocardial p-JNK and p-p38 increased more slowly in SP/SB low dose group, SP/SB high dose group and positive control group (p < 0.05), of which SP/SB high dose group was the slowest (p < 0.05). After four weeks, the total protein and mRNA of myocardial JNK and p38 in all groups had no significant difference (p > 0.05).

 Conclusion: The continuous intravenous injection of SP600125 and SB203580 for four weeks significantly reduced the protein phosphorylation levels of JNK and p38, which provides a practical detective avenue for the long-term study in vivo.