Astragali Radix Combined with Angelicae Sinensis Radix Inhibits Activation of Adventitial Fibroblasts in Rabbit Model of Intimal Hyperplasia via TGF-β1/Smad2 Signaling Pathway
10.13422/j.cnki.syfjx.20222344
- VernacularTitle:黄芪-当归通过TGF-β1/Smad2信号途径抑制兔血管内膜增生模型外膜成纤维细胞的活化作用
- Author:
Xia LI
1
;
Wang CAO
1
;
Changqing DENG
1
Author Information
1. Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardiocerebral Diseases， Hunan University of Chinese Medicine， Changsha 410028， China
- Publication Type:Journal Article
- Keywords:
Astragali Radix;
Angelicae Sinensis Radix;
vascular adventitial fibroblasts;
myofibroblasts;
transforming growth factor-β1 （TGF-β1）/Smad2 signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(3):61-69
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of Astragali Radix combined with Angelicae Sinensis Radix on the activation of adventitial fibroblasts in the rabbit model of intimal hyperplasia and decipher the underlying mechanism. MethodClean white rabbits of the same number of males and females were selected. They were randomly assigned into a sham operation group， a model group， an Astragali Radix group （1 g·kg-1）， an Angelicae Sinensis Radix group （1 g·kg-1）， and Astragali Radix-Angelicae Sinensis Radix groups at the ratios of 1∶1 （Astragali Radix 1 g·kg-1 + Angelicae Sinensis Radix 1 g·kg-1）， 1∶5 （Astragali Radix 1 g·kg-1 + Angelicae Sinensis Radix 5 g·kg-1）， and 5∶1 （Astragali Radix 5 g·kg-1 + Angelicae Sinensis Radix 1 g·kg-1）， and an atorvastatin calcium group （5 mg·kg-1）. The rabbit model of intimal hyperplasia was established by common carotid artery cannula combined with high-cholesterol diet. The sham operation group only underwent the separation operation and not the cannula. The sham operation group had been fed with normal diet and the other groups with high-cholesterol diet （2% cholesterol + 3% olive oil + 95% common diet） since the first day after operation. At the same time， drugs were administrated in corresponding groups， and the sham operation group and model group were administrated with distilled water （15 mL·kg-1） for 28 days. At the end of the experiment， blood was collected from abdominal aorta， and the morphological changes of adventitia were observed by Masson staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in adventitia was detected by immunohistochemical method. The expression of adventitial fibroblast marker vimentin and myofibroblast marker α-smooth muscle actin （α-SMA）， which can reflect the activation of adventitial fibroblasts， was detected by immunofluorescence double staining. Western blot was employed to determine the protein levels of transforming growth factor-β1 （TGF-β1）， Smad2， and p-Smad2. ResultCompared with the normal group， the modeling caused adventitial hyperplasia and up-regulated the expression of TNF-α， IL-1β， α-SMA， Vimentin， TGF-β1， Smad2， and phosphorylation（p）-Smad2 in the injured vessels （P<0.05， P<0.01）. Compared with the model group， Astragali Radix combined with Angelicae Sinensis Radix at the ratios of 1∶1 and 5∶1 alleviated the adventitial hyperplasia and down-regulated the expression of TNF-α， IL-1β， α-SMA， Vimentin， TGF-β1， Smad2， and p-Smad2 （P<0.05， P<0.01）. ConclusionAstragali Radix combined with Angelicae Sinensis Radix， especially at the ratios of 1∶1 and 5∶1， can ameliorate the adventitial hyperplasia in the rabbit model of intimal hyperplasia by inhibiting the transformation of adventitial fibroblasts to myofibroblasts and reducing the local inflammation of blood vessels. The mechanism may be associated with the inhibition of TGF-β1/Smad2 signaling pathway.
