OBJECTIVE:To investigate the effects of Qingshen granules (QSG) on janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in a rat model of unilateral ureteral obstruction (UUO).METHODS:Sixty male Sprague-Dawley rats were randomly divided into six groups,with 10 animals in each group:the untreated sham-operated normal control group;the untreated UUO model control group,the high dose QSG-treated (16 g· kg-1·d-1)UUO group;the medium dose QSG-treated (8 g· kg-1· d-1) UUO group;the low dose QSG-treated (4 g · kg-1 · d-1) UUO group;and the valsartan-treated group (20 mg· kg-1 · d-1).The two untreated control groups received physiological saline (1 mL/100 g per day).All the rats were sacrificed after a 4-week course of treatment.Serum creatinine and leptin;protein expressions of leptin receptor (OB-R),p-JAK2,p-STAT3,nuclear factors-κBp6 (NF-kBp65),and monocytechemotatic protein-1 (MCP-1);mRNA of JAK2,STAT3,calcium-dependent adhesion (E-cadherin),alphasmooth muscle actin (α-SMA) in the kidney tissues;and the expressions of type Ⅳ collagen (Col-Ⅳ) and fibronectin (FN) and the pathomorphology in kidney tissues were treated.RESULTS:Compared with the normal group,the BUN,Scr,and serum leptin levels and the expressions of MCP-1,p-JAK2,p-STAT3,NF-kBp65 and OB-R in renal tissues,and the mRNA expressions of leptin,JAK2 protein,STAT3 protein,α-SMA protein in model group were significantly higher (P ＜ 0.01) in the UUO model group.These parameters were significantly reduced in all the QSG-treated groups and the valsartan-treated group than the UUO model group (P ＜ 0.05 or P ＜ 0.01),with the lowest levels found in the medium dose QSG-treated group (P ＜ 0.05).However,the expression levels of E-cadherin,FN,and Col-Ⅳ in the renal tissues were contrary to the expressions described above.Severe pathological injury was evident in the renal tissues of UUO model rats,which was alleviated in the QSG-treated and valsartan-treated groups,with the least damage found in the medium dose QSG-treated group.CONCLUSION;Our data suggest that the leptin-mediated JAK/STAT signaling pathway is involved in the process of renal interstitial fibrosis in UUO rats.QSG inhibited the activity of the signaling pathway,reduced the activity of NF-kB and inflammatory effect,and the transdifferentiation in the renal tubular epithelial cells.Treatment with QSG may delay the renal fibrosis and protect the renal function from damage following UUO in rats.