β-aminopropionitrile Induced Rodent Model Of Aortic Dissecting Aneurysm And The Pathological Changes

Objective: The aim of this study was to investigate the effect of Lycidyl oxidase inhibitor beta-aminopropylonitrile(BAPN)on the arterial wall of rats,to analyze the gross or pathological changes of the arterial and other tissues of rats treated with BAPN at different concentrations or doses,and to compare with the characteristics of human dissected aneurysm.Methods: 18 SPF SD rats,4-5 weeks,were divided into three groups: SD-0.2(n=6),SD-0.4(n=6),and SD-0.6(n=6).Each group was given 0.2%,0.4%,0.6%BAPN solution as drinking water for seven weeks.40 SPF C57BL6 mices,3 weeks,were randomly divided into four groups of C57-0.2(n = 10),C57-0.4(n = 10),C57-0.6 group and the control group(n = 10),treated with BAPN solution at the concentration of 0.2%,0.4%,0.6% and distilled water as drinking water,respectivelly,for seven weeks.All of experimental animals were free to drink water.The daily water intake was recorded and the weight was measured once a week.The rats that died during the experiment or survived after the experiment were executed and dissected,and then separated their aorta and observed the general changes.Artery was divided into 4 parts of the ascending aorta and descending aorta,abdominal aorta above the renal artery and abdominal aorta under the renal artery,then we intercepted the vascular section as 4μm for HE staining.The vascular diameter,area of the middle membrane and their like were measured with IPP.At the same time,HE staining was managed in aorta from paitents who performed with thoracic surgery with type A dissecting aneurysm,and the pathological changes were observed,compared with the rat aorta with dissecting aneurysms.Results: 1)In C57BL6 mice group,the volume of water collected in control group,c57-0.2,c57-0.4,c57-0.6 group,were 151.30ml/kg/day,144.40 ml/kg/day,150.40 ml/kg/day,114.80ml/kg/day,respectively,which showed a decrease trend with the increase of the concentration of the BAPN solution.In SD rats group,SD-0.2,SD-0.4 and SD-0.6,that were 167.25 ml/kg/day,97.60 ml/kg/day,89.50 ml/kg/day,respectively,and the decline was more obvious.2)In C57-control,C57-0.2,C57-0.4,C57-0.6 group,the average weight of mice aged 9-10 weeks was 22.96,20.78,17.00,19.70 g,respectively.The average weight of SD-0.2,SD-0.4 and SD-0.6 was 142.00,140.00 and 109.00 g respectively.The weight gain of the experimental animals in both genetic background showed a decrease trend with the increase in the concentration of the drug.3)Compared with the control group,C57BL6 mice showed a growth trend in the main artery diameter and the median membrane area in each group,but had no positive correlation with the drug concentration.HE staining of experimental animals showed a membrane thickening of the artery,elastic fiber fracture,disordered arrangement,inflammatory cells infiltration,which accord with the artery pathological changes of human patients with dissecting aneurysm.4)In SD rats,survival rates in groups of SD 0.2,SD-0.4,SD 0.6 aged 4 weeks were 83.3%,50.0% and 83.3% respectively;33.3%,16.7% and 0 at 7 weeks,respectively.In C57 mice,c57-0.2(n=10),c57-0.4(n=10),and c57-0.6(n=10)had a 4-week survival rate of 70.0%,80.0% and 50.0%,respectively,50.0%,40.0% and 40.0% at 7 weeks respectively.In SD rats,no aneurysms occurred after 4 weeks for all groups.After 7 weeks of administration,there were 1,2,and 0 aneurysms in each group.In C57 BL / 6 mice,the incidence of aneurysm in three groups were 10%,20%,20% after 4 weeks of administration,50%,70% and 60% respectively at the end of the experiment.5)In SD rats,the proportion of enteric rupture was 50%,33% and 66% respectively in SD-0.2(n=6),SD-0.4(n=6)and SD-0.6(n=6).There were 0,33% and 33% of each group showed scoliosis.Conclusions: 1.BAPN could significantly affect the water intake of rats or mice and showed a decreasing trend with the increase of drug concentration.2.BAPN could significantly affect the weight gain of rats or mice and showed a decreasing trend with the increase of drug concentration.3.BAPN can cause the thickening of the membrane in the aorta of rats or mice,the elastic protein fracture and permutation disorder,and its pathological changes are similar to the pathological changes of human aneurysms.4.The incidence of dissection aneurysm in C57 mice was much higher than that of SD rats,and the incidence was not significantly correlated with the concentration of the drug.The incidence of aortic aneurysms in the c57-0.4 group was 70%,and the survival rate was 40% in 7 weeks,which could be selected as the ideal animal model for further study.5.In SD rats,the rate of pathological changes in other systems,such as intestinal rupture and scoliosis,was higher than that of the dissection aneurysm,and it was needed to further explore as an animal model of aortic dissection aneurysm.