title: [Biochemical regulatory mechanism of asiaticoside in preventing and treating stent restenosis].
abstract: OBJECTIVE
  To discuss whether asiaticosides could effectively reduce the endothelial cell damage as a biochemical modulator, so as to further inhibit the post-stenting intima-media membrane hyperplasia.
  
  
  METHODS
  Human aortic smooth muscle cells and aortic fibroblasts were selected and divided into the blank group, the rapamycin group and the asiaticoside group and the rapamycin and asiaticoside group. The expressions of muscle cells and fibroblasts TGF-beta1, Smad7 and I-collagen gene were determined by RT-PCR. The expression quantity of I-collagen protein was assayed by ELISA. The coefficient of drug interaction (CDI) between rapamycin and asiaticoside was calculated. Additionally, 16 Chinese mini-swines were randomly divided into group A and group B. One sirolimus drug-eluting stent of the same type was implanted after the high-pressure pre-expansion of anterior descending artery balloon. After the operation, the group A was intravenously injected with normal saline 30 mL x d(-1). Whereas the group B was intravenously injected with asiaticoside 30 mg x kg(-1) x d(-1)(diluted to 30 mL). The expressions of plasma vWF of the two groups were measured at the 7th and 14th days after the operation. At the 28th day after the operation, tissues of the stented vessel segments were sliced and stained to calculate the vessel area, inner stent area, lumen area and neointima area
  
  
  RESULTS
  Compared with the control group, the combination group showed significant up-regulation in smooth muscle cells and fibroblast Smad7 gene, down-regulation in TGF-beta, and obvious inhibition of I-collagen gene expression (P < 0.01). As for smooth muscle cells, there was no difference in the expression of I-collagen between the combination group and the rapamycin group, with CDI at 0. 83. As for fibroblasts, there was a significant difference in the expression of I-collagen between the combination group and the rapamycin group (P < 0.05), with CDI at 0.77. Plasma vWF of the group B was significantly lower than that of the group A (P < 0.05) at the 7th and 14th days after the operation. At the 28th day after the operation, no difference was observed in vessel area and stent area between the two groups. However, the lumen area in the group B was significantly larger than that of the group A(P < 0.05), and the neointima area of the group B was significantly smaller than that of the group A (P < 0.05).
  
  
  CONCLUSIONS
  As an effective biochemical modulator for rapamycin, asiaticosides could inhibit TGF-beta expression, significantly decrease the synthesis and secretion of extracellular matrix, further inhibit the post-stenting intima-media membrane hyperplasia and reduce the endothelial cell damage by effectively up-regulate the expression of Smad7 protein.
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Hou
authors.forename: Ming
authors.initials: M
authors.lastname: Fang
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Chen
authors.forename: Xin-Peng
authors.initials: XP
authors.lastname: Cong
authors.forename: Da-Dong
authors.initials: DD
authors.lastname: Zhang
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D023903:Coronary Restenosis / Q000188:drug therapy / Q000517:prevention & control* / Q000601:surgery; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D015607:Stents / Q000009:adverse effects; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D004365:Drugs, Chinese Herbal; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D003094:Collagen; C004446:asiaticoside