A Novel Method for the Rat Model of Abdominal Aortic Aneurysm Induced by Retroperitoneal Implantation of An Osmotic Pump System with Lipopolysaccharide.

This study tested a novel method for the abdominal aortic aneurysm (AAA) rat model induced by retroperitoneal implantation of an osmotic pump system with lipopolysaccharide (LPS) based on the hypothesis that chronic inflammation of perivascular adipose tissue directly influenced the development and progression of AAAs. 20 Male Sprague-Dawley rats (10-month-old) fed with the Paigen diet were randomly divided into four groups: the blank group ×2, the sham group ×4, the empty capsule group ×4, and the lipopolysaccharide (LPS) capsule group ×10. The LPS capsule group received implantations of the ALZET osmotic pump capsule with LPS (3.6μg/ day) parallel to the abdominal aorta through a retroperitoneal approach. Two weeks later, six rats were randomly selected from the LPS capsule group to form the anti-inflammatory group and received implantations of another osmotic pump capsule with IL-10 (75ng/day) through the same approach. The changes in abdominal aortic diameter were observed by ultrasound every 2 weeks, and samples were harvested for histopathologic and immunohistochemical analysis 6 weeks later. Within the 6 weeks after modeling, the LPS capsule group showed sustained and significant aortic dilatation (p<0.01), while the anti-inflammatory group showed a rapid and obvious shrinkage two weeks after the IL-10 osmotic pump capsule implantation (p<0.01). The LPS capsule group presented excellent pathological mimicking of human AAAs and showed severe medial degeneration with the least elastic content among the five groups at the end of the sixth week (p<0.05). Notably, the anti-inflammatory group showed perfect medial preservation with the most elastic content (p<0.05) and the highest elastin/collagen ratio (p<0.01) at the end of the study. Matrix metalloproteinases 2 and 9 and TLR2 showed strong expression in the LPS capsule group at the end of the sixth week, which was significantly higher than that in the blank group and sham group. Interestingly, the anti-inflammatory group showed a slightly higher MMP9 expression than the LPS capsule group though there was no statistical difference between them. This novel method for the rat AAA model induced by retroperitoneal implantation of an osmotic pump capsule with LPS can concurrently mimic the histological characteristics and natural history of human AAAs. Further studies were needed to improve the osmotic pump system.

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