益气化瘀清热方通过SIRT1/p53/Drp1通路改善局灶节段性肾小球硬化大鼠肾脏损伤的研究OA

Objective To investigate the critical role of the SIRT1/p53/Drp1 signaling pathway in the pathogenesis and progression of focal segmental glomerulosclerosis(FSGS)and to further elucidate the therapeutic mechanism of Yiqi Huayu Qingre Decoction(益气化瘀 清 热 方,YHQD)in FSGS intervention.Methods Forty-two male Sprague-Dawley(SD)rats were randomly divided into seven groups.An FSGS rat model was established by two intravenous injections of doxorubicin.Different doses of YHQD,a SIRT1 receptor agonist(SRT1720),and prednisone were administered as interventions.The 24-hour urinary total protein(24h-UTP),serum albumin(ALB),serum creatinine(Scr),and blood urea nitrogen(BUN)were measured.Renal histopathological changes were assessed by periodic acid-Schiff(PAS)staining under light microscopy.The expression levels of SIRT1,p53,and Drp1 in renal tissues were detected by quantitative real-time PCR(qRT-PCR)and Western blot(WB).Results Compared with the blank control group,the model group exhibited significantly increased levels of 24h-UTP,Scr,BUN,and renal expression of p53 and Drp1(P<0.05),along with significantly decreased ALB and renal SIRT1 expression(P<0.05),accompanied by evident renal pathological injury.In contrast to the model group,all treatment groups showed markedly improved renal histopathology,reduced 24h-UTP,Scr,and renal p53 expres-sion(P<0.05),and elevated ALB levels(P<0.05).Notably,the high-dose YHQD group and the SIRT1 agonist group demonstrated significantly upregulated renal SIRT1 expression(P<0.05)and downregulated Drp1 expression(P<0.05).Conclusion The SIRT1/p53/Drp1 signaling pathway is likely involved in the development of podocyte injury in FSGS.YHQD may ameliorate renal injury in FSGS rats by modulating this signaling pathway.