| Objective:To investigate the characteristics of changes in atherosclerotic vascular remodeling, and the intervention effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on vascular remodeling and its possible intervention mechanisms by qualitative observation and quantitative analysis on the thoracaortae of rabbits after establishing the experimental atherosclerotic model.Methods:A total of 60 male New Zealand rabbits were divided randomly and equally into three groups: C group (control group), As group (atherosclerosis group) and P group (PACAP group). In each group, 5~8 rabbits were sacrificed at the end of the fourth, eighth and twelfth week and the thoracaortae were collected. The segments about 0.5cm long from the initial, middle and terminal part of the above aortae were obtained to make paraffin sections and stained with hematoxylin-eosin(HE), then the sections were observed by light microscope and the related parameters were measured by image analysis system. The rest part of the aortae were stained with Sudan IV and observed with naked eyes. Immunohistochemistry and TUNEL techniques were performed to label a -SM-actin, proliferating cell nuclear antigen (PCNA) and apoptotic cells in the sections from initial segments of each group. And the proliferation index (PI) and apoptosis index (AI) were calculated and compared between P group and As group.Results:1. Qualitative results showed there was no plaque in C group. Plaques both in P group and As group were aggravated gradually accompanying the progression of lesion. Plaque in P group, however, was significantly smaller than that in As group.2. Quantitative morphometric analysis results. (1) Characteristics of changes in As group.Plaque area and percentage of plaque formation increased gradually with theproceeding of experiment in As group, and plaques were mostly located in the initialsegment, decreased in the middle segment and further decreased in the terminal segment(P < 0.05). Lumen area varied rarely in early plaque formation, and decreasedremarkably at the advanced stages (P < 0.05).Meanwhile, both plaque area and lumen area correlated positively with internal elastic laminal area (IELA) and external elastic laminal area (EELA) (P < 0.05). IELA correlated positively with EELA, too (P < 0.01). No correlation were found between plaque area and lumen area (P > 0.05).(2) Results analysis in P group.Plaque area and maximal plaque thickness in P group were smaller than those in As group (P < 0.05), percentage of plaque formation in P group was also lower than that in As group (P < 0.05), but lumen area was larger than that in As group (P < 0.05), even larger than that in C group at the early stage (P < 0.05).3. a -SM-actin immunoreactivity positive cells were located both in tunica media and plaque, but their shape were different. Positive cells in As group migrated gradually to a site near the lumen and formed a cap-like shape, and there was no cap formation in P group.4. Analysis of AI and PI.?Comparison of AI and PI in each group. In As group, PI was higher than AI at the end of the fourth week (P < 0.05), numerical value of AI and PI approximated each other at the end of the twelfth week. In P group, PI was higher than AI at the end of the fourth week (P<0.05), numerical value of PI were still higher than AI at the end of the eighth and twelfth week.(2) Comparison of AI and PI between As group and P group. Both PI and AI in P group were lower than those in As group at the end of the fourth week (P<0.05), numerical value of AI was still lower than PI at the end of the eighth and twelfth week.(3) Both PI and AI in As group and P group showed a rising tendency with the proceeding of experiment, and PI correlated with AI (P<0.05).Conclusions:Vascular remodeling exists during the development of atherosclerotic lesion. PACAP can retard the progression of As by inhibiting negative remodeling and promoting positive remodeling. |
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