Effects of Qingshen granules on Janus Kinase/signal transducer and activator of transcription signaling pathway in rats with unilateral ureteral obstruction

Abstract

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.