ABSTRACT
Objective@#To investigate the effects of tanshinone ⅡA on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E-/- mice model.@*Methods@#Sixteen 8-week-old Apo E-/-male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E-/-+carboxymethyl cellulose per gavage) and the tanshinoneⅡA intervention group (Apo E-/-+30 mg/kg tanshinone ⅡA per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone ⅡA/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR.@*Results@#After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneⅡA intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone ⅡA intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). TanshinoneⅡA intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05).@*Conclusions@#Tanshinone ⅡA could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E-/- mice. The protective effect of tanshinoneⅡA is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.
ABSTRACT
Objective To establish a mouse model of aorta dissection (AD) by β-aminopropionitrile (BAPN) in drinking water + subcutaneously pumped angiotensin II (Ang II) infusion.Methods Forty 3-week-old C57B1/6J male mice were randomly divided into two groups.All animals received 0.1 g/kg/d BAPN in drinking water for 4 weeks.Then the BAPN drinking + saline infusion group and BAPN drinking + Ang II infusion group received continuous saline or Ang II (1,000 ng/kg/min) infusion, respectively, via subcutaneous osmotic minipump for 72 hour.The mice were restricted in a noninvasive computerized tail-cuff system and their arterial systolic blood pressure and heart rate were monitored.Autopsy was performed if a mouse died during the experiment.At the end of the experiment, mice were sacrificed by injection with an overdose of sodium pentobarbital and the aortas were harvested.The formation of aortic false lumen was observed by pathology using hematoxylin-eosin staining.Results The overall incidence of AD in the BAPN drinking administration +Ang II infusion group was 95%, whereas the incidence of AD in the BAPN drinking administration +saline infusion group was only 5%.The mortality from dissecting aneurysm rupture was 24% in the BAPN drinking administration +Ang II infusion group during the experiment.Pathological examination of the aortic cross-sections clearly showed the formation of blood-filled false lumens induced by Ang II.Conclusions A mouse model with high incidence of aortic dissection is successfully established.