Inhibition of experimental abdominal aortic aneurysm in a rat model by way of tanshinone IIA

Background: The purpose of the present study was to investigate whether tanshinone IIA (Tan IIA), one of the major lipophilic components of Salvia miltiorrhiza Bunge, could inhibit the development of elastase-induced experimental abdominal aortic aneurysms (AAAs). Methods: Male Sprague-Dawley rats (n = 12/group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from the Tan IIA and control groups underwent intra-aortic elastase perfusion to induce AAAs, and the rats in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg/rat/d). The maximum luminal diameter of the abdominal aorta was measured before and 5, 12, 18, and 24 d after perfusion. The systolic blood pressure was measured twice using the tail cuff technique before administration and death. Aortic tissue samples were harvested at 24 d and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and Miller's elastin-Van Gieson staining. Results: The rats in the control group had significantly increased aortic sizes compared with the sham group after 24 days (P < 0.05), and the Tan IIA group had a significant reduction in aortic size (Tan IIA versus control, P < 0.05) without affecting blood pressure (P > 0.05). The overexpression of matrix metalloproteinase-2, metalloproteinase-9, monocyte chemotactic protein-1, and inducible nitric oxide synthase and the depletion of elastic fibers and vascular smooth muscle cells induced by elastase perfusion were significantly decreased by Tan IIA treatment (P < 0.05). Conclusions: Tan IIA inhibited the development of elastase-induced experimental AAAs by suppressing proteolysis, inflammation, and oxidative stress and preserving vascular smooth muscle cells. It could be a new pharmacologic therapy for AAAs. (C) 2012 Elsevier Inc. All rights reserved.