基于PI3K/AKT/mTOR信号通路探讨金匮肾气丸治疗慢性肾脏病血管钙化的机制OA

Objective To investigate the mechanism of Jinkui Shenqi pill(JKSQ)in alleviating vascular calcification in chronic kidney disease(CKD)via the Phosphatidylinositol 3-kinase(PI3K)/Protein Kinase B(AKT)/Mammalian Target of Rapamycin(mTOR)signaling pathway.Methods A rat model of CKD with vascular calcification was established by intragas-tric administration of adenine combined with a high-phosphorus diet for 6 weeks.SD rats were randomly divided into six groups:control group,model group,calcitriol group,and JKSQ high-,medium-,and low-dose groups(n=12 per group).After successful modeling,the groups received respective interventions for 4 weeks:the model and control groups received an equal volume of nor-mal saline;the treatment groups received high-,medium-,or low-dose JKSQ or calcitriol via gavage.Serum levels of creatinine(Cr),urea nitrogen(BUN),phosphorus,and tissue calcium were measured.Pathological changes in the abdominal aorta were ob-served,and the expression of key proteins in the PI3K/AKT/mTOR signaling pathway was detected.Results Compared with the control group,the model group showed significantly increased serum Cr,BUN,phosphorus,tissue calcium levels,and the for-mation of abdominal aortic calcified plaques,indicating successful modeling.JSP treatment dose-dependently ameliorated these in-dicators and alleviated vascular calcification.The medium-and high-dose JKSQ groups showed significantly superior effects com-pared to the low-dose group.Notably,the high-dose JKSQ group was comparable to the calcitriol group in reducing Cr levels,whereas calcitriol had no significant effect on serum phosphorus and tissue calcium.Mechanistic studies revealed that JKSQ dose-dependently up-regulated the protein expression of PI3K,p-AKT,and p-mTOR in the abdominal aorta.Conclusion JKSQ may alleviate vascular calcification in chronic kidney disease by activating the PI3K/AKT/mTOR signaling pathway.