Influence of Guishaotongluo on angiogenesis of adventitial vasa vasorum and oxidative stress in early stage of atherosclerosis / 中国药理学通报

ABSTRACT

Aim To observe the effect of Guishao-tongluo ( GSTL ) on the angiogenesis of vasa vasorum and oxidative stress in the early stage of atherosclero-sis. Methods The rabbits ( n =84 ) were randomly divided into 7 groups (n=12)control group,high-fat group, adventitial injury group, GSTL high(GH)and medium ( GM ) dose group, atorvastain group ( ATO ) , and Tongxinluo group ( TXL ) . The normal group was fed with common foodstuffs, and high-fat foodstuffs for the high-fat group to establish an early model of hyper-lipidemia, and all the other groups were fed with high-fat diet combined with carotid artery cannula to build early atherosclerosis carotid artery injury rabbit mod-els. The GSTL high and medium dose was given Guishaotongluo ultrafine powder 4. 16,2. 08 g·kg-1 · d-1 respectively. The atorvastain group and Tongxinluo group were given suspension of atorvastain solution 2. 5 mg·kg-1 ·d-1 , Tongxinluo supermicro powder 0. 6 g ·kg-1 ·d-1 . All groups were treated with gastric per-fusion for 4 weeks. Biochemical method was applied to detect blood lipid change. HE staining was used to ob-serve the pathological morphology of intima-media. Aactivity of serum superoxide dismutase( SOD) ,malon-dialdehyde ( MDA ) content and the total antioxidant capacity ( T-AOC ) in artery serum were detected. NADPH subunits p22phox mRNA, gp91phox mRNA in carotid arteries were located and semi-quantitated by fluorescence in situ hybridization. The expression of VEGF, VEGFR-2 in the carotid artery adventitia was detected by Western blot. Results Compared with normal group,the contents of TC,TG and LDL-C were significantly increased, and VEGF, VEGFR-2 protein levels were remarkly increased in high-fat and adventi-tial injury group. The carotid artery injuries,the degree of angiogenesis of vasa vasorum and NADPH subunits p22phox, gp91phox mRNA in adventitia tissue of the GH,GM, ATO and TXL group were milder in varying degrees compared with those of the vasa injury group. Also the activity of SOD,T-AOC increased,while MDA content,VEGF,VEGFR-2 protein levels were remarkly decreased ( P < 0. 5 or P < 0. 01 ) . Conclusions GSTL can inbibit adventitial neovascularization in the early stage of atherosclerosis, and its mechanism might be related to the increase of total antioxidant capacity of the vascular system and adventitia tissue.