title: Andrographolide inhibits intimal hyperplasia in a rat model of autogenous vein grafts.
abstract: The saphenous vein is considered a common conduit for coronary artery bypass grafting. A major limitation involved is the high graft occlusion rate. We evaluated the effect and mechanism of andrographolide on intimal hyperplasia (IH) of autografted rat veins. For this purpose, 140 female Sprague-Dawley rats were randomly divided into experimental (andro) and control groups. Andro rats received andrographolide (200 mg/kg) lavaged once daily for 2 days before surgery while controls received normal saline. The external jugular vein was grafted into the ipsilateral carotid artery. The animals were killed at 1/3 days and 1/2/4/6/8 weeks postoperatively. The neointima to media area (I/M) ratio was determined. Expression of the p65, E-selectin and MMP-9 proteins/mRNA was also determined. Autografted rat veins displayed IH postoperatively. In andro rats, compared with controls, IH was significantly reduced (P < 0.01) at 2/4/6/8 weeks but not at 1/3/7 days postoperatively. Andrographolide also significantly (P < 0.05) reduced the expression of E-selectin and MMP-9 proteins/mRNAs at 2/4/6/8 weeks postoperatively whereas p65 protein/mRNA was significantly (P < 0.05) diminished at 1/3 days and 1/2/4/6/8 weeks postoperatively as compared with controls. Therefore, it was concluded that andrographolide inhibited IH in autografted rat veins through the suppression of p65, E-selectin, and MMP-9 at the transcriptional level.
authors.affiliation: Department of Cardiovascular Surgery, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Zhi-Tao
authors.initials: ZT
authors.lastname: Zhu
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Jiang
authors.forename: Bai-Chun
authors.initials: BC
authors.lastname: Wang
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Meng
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002339:Carotid Arteries / Q000601:surgery; D001026:Coronary Artery Bypass; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005260:Female; D006965:Hyperplasia; D007601:Jugular Veins / Q000473:pathology / Q000637:transplantation; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D019040:E-Selectin; C030419:andrographolide; D020780:Matrix Metalloproteinase 9