Objective

2

To explore the possible mechanism of

Xintongtai

（心痛泰） in treating atherosclerosis with binding of phlegm and stasis syndrome.

Methods

2

Sixty clean rabbits were randomly divided into sham operation group， model group， fluvastatin group and

Xintongtai

low-， medium- and high-dose groups， with 10 rabbits in each group. Except for the sham operation group， rabbits were given high-fat feeding plus balloon injury of abdominal aorta to establish the vulnerable plaque model of abdominal aorta with binding of phlegm and stasis syndrome. After modelling，

Xintongtai

low-， medium-， and high-dose groups were given

Xintongtai

containing 1.87， 3.73， and 7.46 g/（kg·d） of crude drug by gavage， while the fluvastatin group was given 1.87 mg/（kg·d） of fluvastatin sodium sustained-release tablets by gavage， and the sham operation group and the model group were given intragastric administration of 10 ml/d of ultrapure water， all for 8 weeks. HE staining was used to observe the changes of pathological angiogenesis in vulnerable plaques. The traditional Chinese medicine（TCM） syndrome scale for binding of phlegm and stasis syndrome was used to evaluate the syndromes and calculate the total score. The plaque components including the percentage of extracellular lipids， foam cells， collagen components and smooth muscle cells in the plaque area were measured， and the plaque vulnerability index was calculated. Immunohistochemical method was used to detect the positive expressions of hypoxia-inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF）， vascular endothelial growth factor receptor 2 （VEGFR2）， angiopoietin 2 （Ang-2）， and fibroblast growth factor （FGF） in the plaque tissue. Western blotting was used to detect HIF-1α， VEGF， VEGFR2， Ang-2， FGF protein expression.

Results

2

HE staining showed that there was no plaque in the abdominal aorta in the sham operation group； in the model group， the elastic layer of the arteries was damaged， forming vulnerable plaques， and there were obvious foam cells under the intima， and the fibrous cap of the plaques was ruptured. Compared to those in the model group， the vacuolization of plaque tissue in all

Xintongtai

groups and fluvastatin group was significantly reduced， and the structure of arterial intima and plaque was more stable. All

Xintongtai

groups and the fluvastatin group had lower separate and total TCM scores， decreased extracellular lipids and foam cells， increased collagen components and smooth muscle cells in the plaque area， decreased plague vulnerability index， and lower positive expression and protein expression of HIF-1α， VEGF， VEGFR2， Ang-2， and FGF in plaque tissue than the model group （

P

＜0.05 or

P

＜0.01）； and more improvements were found in the medium- and high-dose

Xintongtai

groups and the fluvastatin group than the low-dose

Xintongtai

group （

P

＜0.01）. There was no statistically significant differences in all indicators between any two of the

Xintongtai

medium-， high-dose groups and fluvastatin group （

P

＞0.05）.

Conclusion

2

Xintongtai

may reduce pathological angiogenesis and stabilize vulnerable plaques by down-regulating the HIF-1α/VEGF/VEGFR2 signaling pathway in plaque tissue， thereby improving the binding of phlegm and stasis syndrome in atherosclerosis.