Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways

Total Panax notoginseng saponin (TPNS) is the main bioactivity compound derived from the roots and rhizomes of Panax notoginseng (Burk.) F.H. Chen. The aim of this study was to investigate the effectiveness of TPNS in treating vascular neointimal hyperplasia in rats and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups, sham (control), injury, and low, medium, and high dose TPNS (5, 10, and 20 mg/kg). An in vivo 2F Fogarty balloon-induced carotid artery injury model was established in rats. TPNS significantly and dose-dependently reduced balloon injury-induced neointimal area (NIA) (P<0.001, for all doses) and NIA/media area (MA) (P<0.030, for all doses) in the carotid artery of rats, and PCNA expression (P<0.001, all). The mRNA expression of smooth muscle (SM) α-actin was significantly increased in all TPNS groups (P<0.005, for all doses) and the protein expression was significantly increased in the medium (P=0.006) and high dose TPNS (P=0.002) groups compared to the injury group. All the TPNS doses significantly decreased the mRNA expression of c-fos (P<0.001). The medium and high dose TPNS groups significantly suppressed the upregulation of pERK1/2 protein in the NIA (P<0.025) and MA (P<0.004). TPNS dose-dependently inhibited balloon injury-induced activation of pERK/p38MAPK signaling in the carotid artery. TPNS could be a promising agent in inhibiting cell proliferation following vascular injuries.

三七总皂苷（Total Panax notoginseng saponin, TPNS）是源自三七（Panax notoginseng (Burk.) F.H. Chen）根与根茎的主要活性成分。本研究旨在探究TPNS治疗大鼠血管内膜增生（vascular neointimal hyperplasia）的效果及其作用机制。将雄性Sprague-Dawley大鼠随机分为5组：假手术组（对照组）、损伤模型组以及低、中、高剂量TPNS组（给药剂量分别为5、10、20 mg/kg）。通过2F Fogarty球囊建立大鼠颈动脉（carotid artery）损伤体内模型。实验结果表明：TPNS可显著且呈剂量依赖性地降低大鼠颈动脉球囊损伤后的内膜面积（neointimal area, NIA）（各剂量组P<0.001）与内膜面积/中膜面积（media area, MA）比值（各剂量组P<0.030），同时显著下调增殖细胞核抗原（Proliferating Cell Nuclear Antigen, PCNA）的表达（所有组P<0.001）。各TPNS给药组的平滑肌α肌动蛋白（smooth muscle α-actin）mRNA表达水平均显著升高（各剂量组P<0.005）；与损伤模型组相比，中剂量（P=0.006）与高剂量（P=0.002）TPNS组的平滑肌α肌动蛋白蛋白表达水平亦显著升高。所有TPNS给药组的c-fos基因mRNA表达水平均显著降低（P<0.001）。中、高剂量TPNS组可显著抑制损伤区域内膜与中膜内pERK1/2蛋白的上调表达（内膜区域P<0.025，中膜区域P<0.004）。TPNS可呈剂量依赖性地抑制大鼠颈动脉球囊损伤后pERK/p38丝裂原活化蛋白激酶（p38 Mitogen-Activated Protein Kinase, p38MAPK）信号通路的激活。综上，TPNS有望成为抑制血管损伤后细胞增殖的潜在治疗制剂。