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.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Tao
T
Shang
Zhao
Z
Liu
Min
M
Zhou
Christopher K
CK
Zarins
Chengpei
C
Xu
Chang-jian
CJ
Liu
D045784:Abietanes / Q000627:therapeutic use*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; C021751:tanshinone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9