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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

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Journal of Traditional Chinese Medicine 2024年第3期44卷 458-467页

作者： GAO Xiaomeng QIANG Panpan CHANG Jingyue FAN Lili YANG Fan XU Qingyou Graduate School Hebei University of Chinese Medicine Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns Hebei University of Chinese Medicine Institute of Integrative Medicine Hebei University of Chinese Medicine

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 VEGFAinduced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

关键词： aldosterone epithelial-mesenchymal transition eplerenone huoxue jiedu huayu recipe mineralocorticoid receptors unilateral ureteral obstruction

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huoxue jiedu huayu recipe(活血解毒化瘀方)alleviates contralateral renal fibrosis in unilateral ureteral obstruction rats by inhibiting the transformation of macrophages to myofibroblast

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Journal of Traditional Chinese Medicine 2023年第1期43卷 105-112页

作者： XIONG Yunzhao LIU Lingjin LIU Ziqian CHEN Gege HAO Juan GAO Xiaomeng QIANG Panpan WANG Zheng XU Qingyou Graduate School Hebei University of Chinese MedicineHebei Key Laboratory of Integrative Medicine on Liver-Kidney PatternsHebei University of Chinese MedicineHebei University of Chinese MedicineShijiazhuang 050091China Graduate School Hebei University of Chinese Medicine Hebei Key Laboratory of Integrative Medicine on Liver-Kidney PatternsHebei University of Chinese MedicineShijiazhuang 050091China Graduate School Hebei University of Chinese MedicineHebei Key Laboratory of Integrative Medicine on Liver-Kidney PatternsHebei University of Chinese MedicineDepartment of Internal MedicineHebei University of Chinese MedicineShijiazhuang 050091China

OBJECTIVE:To investigate the action and underlying mechanisms of huoxue jiedu huayu recipe(活血解毒化瘀方,HJHR)against unilateral ureteral obstruction(UUO)-induced injury in the contralateral kidney.METHODS:Forty-eight male Sprague-Dawley rats weighing(200±10)g were used in this study and randomly assigned to 4 groups:a sham group,a UUO group,a UUO+eplerenone(EPL)group,and a UUO+HJHR group.The contralateral kidneys were harvested for further study 180 d after surgery.Histological analysis,immunohistochemistry and immunofluorescence were used to study the fibrosis of the contralateral kidneys obtained from UUO rats.Contralateral kidney damagerelated pathway proteins were detected by real-time polymerase chain reaction and Western blot analysis.RESULTS:HJHR significantly inhibited fibrosis of the contralateral kidney in UUO rats by attenuating the UUOinduced macrophage-to-myofibroblast transition(MMT)in the contralateral kidney.Moreover,HJHR attenuated fibrosis in the contralateral kidney of UUO rats by preventing MMT through the aldosterone/mineralocorticoid receptor/serum/glucocorticoid regulated kinase 1 pathway.CONCLUSIONS:Our findings suggest that HJHR may be a potential treatment for renal interstitial fibrosis of obstructive nephropathy.

关键词： ureteral obstruction renal fibrosis aldosterone receptors,mineralocorticoid macrophages myofibroblast huoxue jiedu huayu recipe

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