Prolonged exposure of the peritoneum to high
glucose dialysate leads to the development of
peritoneal fibrosis (PF), and apoptosis of peritoneal mesothelial cells (PMCs) is a major cause of PF. The aim of this study is to investigate whether
Astragaloside IV could protect PMCs from apoptosis and alleviate PF. PMCs and rats PF models were induced by high
glucose peritoneal fluid. We examined the pathology of rat peritoneal tissue by HE staining, the thickness of rat peritoneal tissue by Masson's staining, the number of mitochondria and oxidative stress levels in peritoneal tissue by
JC-1 and DHE fluorescence staining, and mitochondria-related
proteins and apoptosis-related
proteins such as PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 were measured. We used hoechst staining and flow cytometry to assess the apoptotic rate of PMCs in the PF model, and further validated the observed changes in the expressions of PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 in PMCs. We further incubated PMCs with
MG-132 (
proteasome inhibitor) and
Cyclohexylamine (
protein synthesis inhibitor). The results demonstrated that
Astragaloside IV increased the expression of PGC-1α by reducing the ubiquitination of PGC-1α. It was further found that the protective effects of
Astragaloside IV on PMCs were blocked when PGC-1α was inhibited. In conclusion,
Astragaloside IV effectively alleviated PF both in vitro and in vivo, possibly by promoting PGC-1α to enhance mitochondrial synthesis to reduce apoptotic effects.