Effect of Yishen Huoxue Prescription on Endothelial Structure and Function in Mice with Renal Interstitial Fibrosis
10.13422/j.cnki.syfjx.20220901
- VernacularTitle:益肾活血方对肾纤维化小鼠血管内皮结构及功能的影响
- Author:
Jian ZHONG
1
;
Fang LUO
2
;
Guiyu FANG
2
;
Dengyong LU
2
;
Xiaodong SHI
2
;
Huimin WU
2
;
Xueying WENG
2
;
Yushan CHEN
2
;
Jinjin ZUO
2
Author Information
1. The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China
2. Graduate School of Guangxi University of Chinese Medicine,Nanning 530001,China
- Publication Type:Journal Article
- Keywords:
Yishen Huoxue prescription;
unilateral ureteral obstruction (UUO) mice;
renal interstitial fibrosis;
endothelial cells
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(15):70-77
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis (RIF) from the perspective of endothelial cell and cell energy metabolism. MethodThe model was successfully established by unilateral ureteral obstruction (UUO). Seventy-five SPF C57BL/6 mice were randomly divided into a model group, a resveratrol group (50 mg·kg-1·d-1), three Yishen Huoxue prescription low, medium, and high-dose groups (7.1, 14.2, 28.4 g·kg-1·d-1), with 15 mice in each group. In addition, another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7, 14, and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 (CD31) was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin (α-SMA), collagen Ⅳ (Col-Ⅳ), angiopoietin 1(Ang-1) and tyrosine kinase receptors 2 (Tie-2), vascular endothelial growth factor (VEGF), vascular endothelial cadherin (VE-cadherin), and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the levels of reactive oxygen species (ROS) in mice were detected by enzyme linked immunosorbent assay (ELISA). ResultAs compared with the sham operation group, the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time (P<0.05), α-SAM and Col-Ⅳ protein expression levels were significantly increased (P<0.01), but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased (P<0.01), and the protein and mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin were significantly down-regulated (P<0.01). As compared with the model group, the expression of CD31 was increased (P<0.05), and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased (P<0.01). The ROS content was significantly decreased (P<0.01), and the protein and mRNA expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin were up-regulated (P<0.01), As compared with the resveratrol group, the protein expressions of Ang-1/Tie-2, VEGF, VE-cadherin, and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different (P<0.01). There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group, and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group. ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair, regulating mitochondrial ROS to reduce oxidative stress, protecting the integrity of renal endothelial structure, delaying cell apoptosis, and maintaining cell energy metabolism.