吡格列酮缓解小鼠牙周炎相关肾损伤的作用及其与Klotho的关系OA

Objective This study aims to examine the protective effect of the peroxisome proliferator-activated receptor gamma(PPAR-γ)agonist pioglitazone on renal injury linked to periodontitis in mice and to preliminarily explore the relationship between this effect and Klotho.Methods A total of 24 eight-week-old C57 mice were random-ly assigned to three groups:control(C),periodontitis(P),and pioglitazone treatment(P+Pio).Silk ligation was employed to induce experimental periodontitis around the maxillary second molars,and pioglitazone was administered through oral gavage.After eight weeks,the mice were euthanized.The maxillae were subjected to Micro-CT scanning.Periodontal and kidney tissues underwent hematoxylin and eosin,periodic acid-Schiff,and Masson's trichrome staining.Renal ultra-structure was observed using transmission electron microscopy(TEM),and malondialdehyde(MDA),superoxide dis-mutase(SOD),and glutathione(GSH)were measured.The levels of renal reactive oxygen species(ROS)were assessed through MitoSOX red fluorescence staining.Serum concentrations of creatinine(Cre),blood urea nitrogen(BUN),and al-bumin(Alb)were evaluated,in addition to urinary protein levels.The gene and protein expression levels of PPAR-γ,Klotho,phosphatidylinositol 3-kinase(PI3K),and serine/threonine kinase(AKT)were determined using quantitative re-verse transcription polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC).Results Micro-CT and periodontal histological analysis indicated substantial alveolar bone loss and heightened periodontal pocket depth in the second molar region of the P group relative to the C group.The P+Pio group exhibited reduced effects,compared with the P group.Histological examination of renal tissue and TEM revealed pathological damage in the P group.Pathological damage was alleviated in the P+Pio group.Biochemical assays and MitoSOX staining indicated that the P group demon-strated lower levels of SOD and GSH levels than the C group and increased MDA and ROS levels.Compared with the P group,the P+Pio group exhibited elevated levels of SOD and GSH and reduced levels of MDA and ROS.No notable dif-ferences were detected in Cre,BUN,and Alb levels across the groups.qRT-PCR and IHC revealed a reduction in PPAR-γ and Klotho expression levels in the renal tissues and an increase in PI3K and AKT expression levels in the P group com-pared with the C group.In the P+Pio group,the expression levels of PPAR-γ and Klotho were elevated relative to those of the P group,whereas expression levels of PI3K and AKT were decreased.Conclusion Pioglitazone can alleviate re-nal damage associated with periodontitis in mice,and its effect may be related to the upregulation of Klotho expression.