Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model

Objective: To investigate the effect and potential mechanisms of rutaecarpine(Rut) in a rat artery balloon-injury model. Methods: The 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 m RNA expressions of c-myc, extracellular signal-regulated kinase 2(ERK2), MAPK phosphatase-1(MKP-1) and endothelial nitric oxide synthase(e NOS) 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(c GMP) were also determined. Results: Compared 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 m RNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of e NOS 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 c GMP in the plasma(P<0.05 or P<0.01). Conclusion: Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.