Abstract:

ABSTRACT Objectives: To investigate the effects of Astragaloside IV (AS-IV) on the apoptosis of renal tubular epithelial cells induced by transforming growth factor-β1 (TGF-β1). Methodology: In vitro, normal human renal tubular epithelial cells (HK 2) were stimulated with recombinant TGF -β1 (10 ng/ml) and simultaneously treated with different concentrations of AS-IV (50, 100, and 200 μg/ml) for 24 h. In vivo, the unilateral ureteral obstruction (UUO) model was constructed. Mice in AS?IV group were orally administrated AS -IV 20mg ?kg-1 ?d-1for 7 days after operation, and mice in other groups were administrated the equal volume vehicle. Bilateral kidneys were collected on the 14th day after operation. Western blot was used to detect the expression levels of cleaved caspase 3, c-Jun N-terminal kinase (JNK) and p-JNK. Cell viability was determined by a cell count kit and apoptosis was estimated by TUNEL staining. Results: Cell viability was significantly inhibited and cell apoptosis was increased by TGF-β1 stimulating for 24h, while those phenomenon were notably attenuated by AS-IV treatment, and the 200μg/ml AS-IV was the optimal effect (P<0.01). The proteins expression of TGF-β1 and cleaved caspase 3 were increased significantly in UUO kidney tissues (P<0.01), which was also reversed by AS-IV administration (P<0.01). AS-IV inhibited JNK MAPK signals both in vivo and in vitro (P<0.01). Conclusion: AS-IV could attenuate the apoptosis of renal tubular epithelial cells induced by TGF-β1. The mechanism of AS-IV protective effect might be associated with inhibition of JNK MAPK phosphorylation.

Key words: Astragaloside IV, transforming growth factor-β1, apoptosis, c-Jun N-terminal kinase