摘要
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 wererandomly 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 gdm dose QSG-·kg-1-1) UUO group; the mediutreate·d(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 m L/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-k Bp65), and monocytechemotatic protein-1(MCP-1); m RNA of JAK2, STAT3, calcium-dependent adhesion(E-cadherin), alphasmooth muscle actin(α-SMA) in the kidney tissues;and the expressions of type ronectin(FN) and the pⅣat collagen(Col-homorphologyⅣ)and fib 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-k Bp65 and OB-R in renal tissues, and the m RNA 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. Se-vere 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-k B 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.
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 wererandomly 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 gdm dose QSG-·kg-1-1） UUO group; the mediutreate·d（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 m L/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-k Bp65）, and monocytechemotatic protein-1（MCP-1）; m RNA of JAK2, STAT3, calcium-dependent adhesion（E-cadherin）, alphasmooth muscle actin（α-SMA） in the kidney tissues;and the expressions of type ronectin（FN） and the pⅣat collagen（Col-homorphologyⅣ）and fib 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-k Bp65 and OB-R in renal tissues, and the m RNA 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. Se-vere 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-k B 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.
基金
Supported by the National Natural Science Foundation of China(Based on JAK/STAT Signaling Pathway to Discuss the Effects of Qingshen Granules for Anti Renal Fibrosis,General Program,No.81473673
Based on P-selectin/PSGL-1 mediated MAPK Signaling Pathway to Discuss the Effects of Qingshen granules for Vascular Endothelial Injury Due to Renal Fibrosis,General Program,No.81673931)
National Science Fund for Distinguished Young Scholars of China(Based on NF-k B Signaling Pathway and Oxidative Stress to Discuss the Effects of Qingshen granules in Transdifferentiation of Renal Tubular Epithelial Cells,No.81403372)
Anhui Natural Science Foundation(Based on Leptin-JAK/STAT-inflammatory pathway to study the effects of Qingshen granules for anti renal fibrosis,No.1508085MH198)
