The Experimental Study Of The Intervenient Effects Of Neuropeptide PACAP On Rabbits Atherosclerosis Development

Object:This study was aimed to investigate the intervenient effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on experimental atherosclerotic rabbits and its possible antiatherogenetic mechanisms.Methods:A total of 70 rabbits were randomly separated into 3 groups, group C (control group), group AS [atherosclerosis (AS) model group] and group P (PACAP group). Prior to, and the end of 4th, 8th and 12th weeks, the weights of rabbits were recorded, blood samples were obtained for serum malonyldialdehyde (MDA) and nitric oxide (NO) assay. Meanwhile, in each group 5~8 rabbits were sacrificed and the aortas were harvested. The aortae were stained with Sudan IV and hematoxylin-eosin (HE) respectively, then surveyed the pathological changes by the naked eyes and light microscope. Endothelin (ET) and vascular endothelial growth factor (VEGF) were studied with immunohistochemical techniques at the different stages of rabbits AS progression. Morphometric analysis was performanced on the relative area of AS lesions, residual luminal area, average and maximal neointima thickness.Results:(1) AS lesions were not showed in group C, while both in group AS and group P the lesions were aggravating during the progression of AS. The degree of pathology was less serious in group P than in group AS.(2) Compared with the group C, MDA in serum of group AS and group P were remarkably increased. The level of MDA was gradually elevated in group AS but not in group P. There was a significant difference between group AS andgroup P.(3) The content of NO in group P was obviously higher than that of group AS .(4) The extent of ET immunoreactivity in group P was weaker than that of group AS at the end of 12th week.(5) VEGF expression was intensified gradually as the pathology developed both in group AS and group P. There was no substantial difference between two groups.Conclusions:PACAP has retarded the development of AS and alleviated the degree of atheromatous lesions. PACAP have good effects against AS in vivo, the possible mechanisms maybe related to inhibition of lipoperoxidation, increasion of NO production and reduction of ET secretion.