Expression of down-regulated adipokine Chemerin by Tripterygium glycosides in obstructive nephropathy

Abstract

Objective To investigate the expression and significance of Chemerin, an adipokin, in the renal interstitial fibrosis model of rats with unilateral ureteral obstruction (UUO) and the effect of immunosuppressant Tripterygium glycosides (TWP) for intervention. Methods A total of 72 clean and healthy SD male rats were randomly divided into four groups: A (sham operation group) , B (UUO-model group) ; C (UUO-model with low-dose TWP intervention group) and D (UUO-model with high-dose TWP intervention group) . On day 1 of modeling, group C was ad ministered with TWP (10 mg·kg-1·d-1) by gavage, group D was ad ministered with TWP (20 mg·kg-1·d-1) by gavage, and the other two groups were ad ministered with the same volume of normal saline. Six rats in each group were randomly included and sacrificed at the 3, 7, and 14d after the operation, and the renal tissues were taken for exa mination. The HE and Masson staining were used to deter mine the pathological changes of the renal tissues. Immunohistochemistry and Western Blot were used to exa mine the expression of Chemerin in the modeling side at kidney of each group. Results The findings of HE and Masson staining showed that the renal structure was normal, and there was no obvious pathological change in renal tubules and renal interstitium in group A. Compared with the contemporary group A, the number of dilated tubules significantly increased, a large number of inflammatory cells in renal interstitium infiltrated, the width of interstitium increased, the fibrosis changed, and the colored collagen fibers in the widened interstitial region increased. The findings of immunohistochemistry and Western Blot showed that the expression of Chemerin and TGF-β1 in group B was the highest (P<0.05) , and there were statistically significant differences among the groups (P<0.05) . In groups C and D, the renal tubulointerstitial damage and Chemerin expression level significantly decreased compared with those in the contemporary group B (P<0.05) , but still higher than those in the contemporary group A (P<0.05) . The contemporary groups C and D were compared. The renal tubulointerstitial damage and Chemerin expression level in group D significantly decreased compared with those in group D (P<0.05) . Conclusions The adipokine Chemerin is involved in the development of renal interstitial fibrosis induced by UUO, and its expression gradually increases along with the aggravating severity of renal interstitial damage, suggesting that it may promote renal interstitial fibrosis. TWP may down-regulate the expression of Chemerin in the tubulointerstitium, thereby inhibiting the TGF-β1 pathway and protecting the kidney, thus effectively reducing renal interstitial fibrosis. A short-term observation shows that the effect of TWP is dose-dependent. Key words: Kidney failure; Transfor ming growth factor beta; Collagen type Ⅲ; Tripterygium glycosides