山柰酚调节线粒体自噬改善高糖作用下足细胞损伤OA

Objective To investigate the protective effect and molecular mechanism of kaempferol on high glucose-induced injury in MPC-5 cells in vitro.Methods Transmission electron microscopy was used to observe ultrastructural changes in mitochondria and endoplasmic reticulum in each group.Differentially expressed proteins were identified by proteomics,and KEGG and GO enrichment analyses were performed,and autophagy-related proteins were verified by Western blotting.Results In the high glucose group,cells showed ultrastructural alterations including mitochondrial swelling,vacuolization and cristae loss,as well as endoplasmic reticulum dilation and ribosome detachment.In the kaempferol-treated group,mitochondrial swelling and vacuolization were alleviated;Double-membraned autophagosomes encapsulating damaged mitochondria and autolysosomes were observed,and endoplasmic reticulum dilation was attenuated.A total of 57 significantly differentially expressed proteins were screened between the high glucose group and the kaempferol intervention group.Among them,Serpin H1,MTX1 and PDIA6—marker proteins localized to the mitochondrial outer membrane and endoplasmic reticulum—were markedly reversed.Mitophagy,endoplasmic reticulum protein processing,and the PI3K-Akt signaling pathway were significantly enriched.Kaempferol significantly regulated the expression levels of key autophagy-related proteins including PI3K,LC3 and PINK1.Conclusion Kaempferol may reduce podocyte injury by activating mitochondrial autophagy and stabilizing the intracellular microenvironment.Serpin H1,MTX1 and PDIA6 may serve as marker proteins for kaempferol-mediated amelioration of podocyte injury.