Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model.
- Author:
Yang XU
1
;
Xiu-Ping CHEN
2
;
Feng ZHANG
1
;
Hua-Hua HOU
1
;
Jing-Yi ZHANG
1
;
Shu-Xian LIN
1
;
An-Sheng SUN
3
Author Information
- Publication Type:Journal Article
- Keywords: balloon-injury; extracellular signal-regulated kinase 2; intimal hyperplasia; nitric oxide; rutaecarpine
- MeSH: Actins; metabolism; Animals; Carotid Arteries; drug effects; metabolism; pathology; Carotid Artery Injuries; drug therapy; genetics; pathology; Cyclic GMP; blood; Disease Models, Animal; Gene Expression Regulation; drug effects; Hyperplasia; Indole Alkaloids; pharmacology; therapeutic use; Male; Nitric Oxide; blood; Phosphorylation; drug effects; Proliferating Cell Nuclear Antigen; metabolism; Quinazolines; pharmacology; therapeutic use; RNA, Messenger; genetics; metabolism; Rats, Sprague-Dawley; Tunica Intima; drug effects; pathology
- From: Chinese journal of integrative medicine 2018;24(6):429-435
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.
METHODSThe intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen (PCNA) and smooth muscle (SM) α-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 (ERK2), MAPK phosphatase-1 (MKP-1) and endothelial nitric oxide synthase (eNOS) were determined by real-time reverse transcription-polymerase chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. The plasma contents of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) were also determined.
RESULTSCompared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury (P<0.05 or P<0.01). The positive expression rate of PCNA was decreased, while the expression rate of SM α-actin obviously increased in the vascular wall after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01). Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated (P<0.05 or P<0.01). The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downregulated after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01), respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma (P<0.05 or P<0.01).
CONCLUSIONRut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.
