ABSTRACT
Objective: To investigate the effects of asragaloside IV (AS-IV) on cultured vascular smooth muscle cells (VSMCs) and neointima hyperplasia in the carotid artery of rats after ballon injury and explore the inhibitory mechanisms. Methods: For next related researches, primary cultures of VSMCs were prepared from the thoracoabdominal aorta of rats using explant method. Taking the recombinant rat tumor necrosis factor (TNF-α, 100 ng/mL ) as the stimulating factor, the model of VSMCs proliferation was established by TNF-α inducer in vitro and the effects of AS-IV (0, 0.5, 5, 25, and 50 μg/mL) on the VSMCs proliferation induced by TNF-α were determined by CCK-8 method. Rat carotid artery balloon injury model was prepared by Fogarty (2F) balloon catheter. Fifty healthy male Sprague-Dawley rats were randomly divided into five groups: a Sham-operation group (Sham), a model group (model), and three AS-IV-treated (20, 40, and 60 mg/kg) groups. Three days before the surgery, 1% CMC, AS-IV 20, 40, and 60 mg/kg were ig administered to each group once daily for continuous 17 d. Fifteen days after the surgery, rats were killed, and the carotid arterys were harvested. Hematoxylin-elsin staining was carried out to observe the pathomorphological change in vascular intima. The measurement of lumen area, intimal area, intimal area/medium film area were measured by computer image analysis system; Immunohistochemistry staining was performed to measure the expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor-BB (PDGF-BB). Results: The proliferative activity of VSMCs was obviously increased in the TNF-α group under the stimulation of TNF-α. There was a significant difference compared with the control group (P < 0.01). However, when pretreated with AS-IV ahead of time, we found that AS-IV significantly inhibited TNF-α-induced VSMCs proliferation in a dose- and time-dependent manner compared to the TNF-α group. Compared with the model group, the area of intima, the ratio of intima to media (I/M), and the expression of PCNA and PDGF-BB decreased significantly (P < 0.05) in AS-IV groups. Conclusion: AS-IV exerts the inhibitory effects on VSMCs proliferation in a dose- and time-dependent manner. AS-IV significantly inhibits the neointimal hyperplasia in rat carotid artery. It might be partially attributed to the inhibition of proliferation. It may be one of the mechanisms of inhibiting the proliferation of carotid intima in rats induced by balloon injury that AS-IV inhibits the expression of growth factor PDGF-BB.