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

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Key Laboratory of Basic Pharmacology of Guizhou and Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou Province, 563099, China

    Yang Xu, Feng Zhang, Hua-hua Hou, Jing-yi Zhang, Shu-xian Lin & An-sheng Sun

  2. Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

    Yang Xu

  3. Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China

    Xiu-ping Chen

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  1. Yang Xu
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  2. Xiu-ping Chen
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  3. Feng Zhang
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  4. Hua-hua Hou
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  5. Jing-yi Zhang
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  6. Shu-xian Lin
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  7. An-sheng Sun
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Correspondence to An-sheng Sun.

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Xu, Y., Chen, Xp., Zhang, F. et al. Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model. Chin. J. Integr. Med. 24, 429–435 (2018). https://doi.org/10.1007/s11655-017-2900-3

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  • DOI: https://doi.org/10.1007/s11655-017-2900-3

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