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Huoxue Jiedu Huayu recipe (活血解毒化瘀方) inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats
Received date: 2023-02-10
Accepted date: 2023-07-07
Online published: 2024-04-30
Supported by
Natural Science Foundation-funded Project: Effect of Macrophage-to-Myofibroblast Transition in Contralateral Kidney of Unilateral Ureteral Obstruction Rats Through the Aldosterone/MR/SGK1 Pathway and Inhibition of Chinese Herbs(81873251);Natural Science Foundation-funded Project: Aldosterone Stimulates MR Activation to Induce Lymphangiogenesis in the Contralateral Kidney of UUO Rats and the Protective Effect of Yiqi Jiedu Huayu Herbs(82174317);Hebei Provincial Postgraduate Innovative Ability Cultivation Funding Project: Aldosterone Induced Macrophages to Secrete VEGFA to Participate in Renal Angiogenesis and the Protective Effect of Huoxue Jiedu Huayu Recipe(CXZZBS2023140);Construction Program of New Research and Development Platform and Institution, Hebei Province Innovation Ability Promotion Plan under Grant(20567624H)
OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe (活血解毒化瘀方, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction (UUO) rats and the mechanism by which it reduces of renal fibrosis.
METHODS: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected.
RESULTS: HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited.
CONCLUSIONS: These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
Xiaomeng GAO , Panpan QIANG , Jingyue CHANG , Lili FAN , Fan YANG , Qingyou XU . Huoxue Jiedu Huayu recipe (活血解毒化瘀方) inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats[J]. Journal of Traditional Chinese Medicine, 2024 , 44(3) : 458 -467 . DOI: 10.19852/j.cnki.jtcm.20240423.005
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