Yang Xu1,2, Xiu-Ping Chen3, Feng Zhang1, Hua-Hua Hou1, Jing-Yi Zhang1, Shu-Xian Lin1, An-Sheng Sun4. 1. Key Laboratory of Basic Pharmacology of Guizhou and Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou Province, 563099, China. 2. Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China. 3. Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China. 4. Key Laboratory of Basic Pharmacology of Guizhou and Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou Province, 563099, China. sunansheng1945@163.com.
Abstract
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 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. 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 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). 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.
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 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. 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 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). 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.
Authors: William H Thiel; Carla L Esposito; David D Dickey; Justin P Dassie; Matthew E Long; Joshua Adam; Jennifer Streeter; Brandon Schickling; Maysam Takapoo; Katie S Flenker; Julia Klesney-Tait; Vittorio de Franciscis; Francis J Miller; Paloma H Giangrande Journal: Mol Ther Date: 2016-01-06 Impact factor: 11.454
Authors: Melissa E Hogg; Vinit N Varu; Ashley K Vavra; Daniel A Popowich; Monisha N Banerjee; Janet Martinez; Qun Jiang; Joseph E Saavedra; Larry K Keefer; Melina R Kibbe Journal: Free Radic Biol Med Date: 2011-01-21 Impact factor: 7.376
Authors: S Janssens; D Flaherty; Z Nong; O Varenne; N van Pelt; C Haustermans; P Zoldhelyi; R Gerard; D Collen Journal: Circulation Date: 1998-04-07 Impact factor: 29.690
Authors: Pey-Jen Yu; Giovanni Ferrari; Luigi Pirelli; Iosif Gulkarov; Aubrey C Galloway; Paolo Mignatti; Giuseppe Pintucci Journal: Cell Signal Date: 2007-03-15 Impact factor: 4.315