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

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 ofα-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 andα-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.

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

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.