Abstract:Objective: This study was to determine the effect of the Bushen Kangshuai tablet on nitric xidesynthase (NOS) /nitric oxide (NO) -cyclooxygenase-2 (COX-2) pathway and its associated protein nitrative modification influence in atherosclerotic rabbits. Method: Fifty-six rabbits were randomly divided into normal group, model group, Bushen Kangshuai tablet therapeutic group (1 g·kg-1·d-1) and simvastatin therapeutic group (5 mg·kg-1·d-1). The blood sample of all animals were collected before administration, after supplementing with the 8 weeks, 12 weeks and 16 weeks, the animals were sacrificed under aseptic conditions. Aortic iNOS mRNA, p38-mitogen activated protein kinase (p38 MAPK) mRNA expression was measured by Q-PCR method, the serum COX-2 activity and NO, 3-nitrotyrosine (3-NT) levels were measured by ELISA, and eNOS protein level was detected by western blot analysis. Result: iNOS expression and protein tyrosine nitration could be detected in different periods of atherosclerosis, model group showed intimal thickening, thin fibrous cap, a large lipid plaque deposition. Significant ieduction of serum 3-NT levels was found when atherosclerosis occured, but Bushen Kangshuai tablets could decreased the expression of serum 3-NT levels, NO levels were significantly increased, while COX-2 activity did not change significantly. Bushen Kangshuai tablets significantly reduced the rabbit p38 MAPK levels. The model group showed a significant increase in iNOS and p38 MAPK gene expression. The simvastatin had a similar inhibitory effect of nitration. Conclusion: Bushen Kangshuai tablets in atherosclerotic lesions plays an important role in anti-nitration, the protective mechanism may regulate p38 MAPK mRNA, iNOS mRNA gene expression and iNOS/NO-COX-2 pathway related enzymes possibly through anti-nitration reaction to stabilize of the atherosclerotic plaques.
