雷公藤多苷通过调控AHR信号通路缓解膜性肾病大鼠肾组织氧化应激和炎症的作用机制OA

Objective To investigate the mechanism of glycosides of Tripterygium wilfordii(GTW)in alleviating oxidative stress and inflammation in renal tissue of rats with membranous nephropathy(MN)by modulating the aryl hydrocarbon receptor(AHR)signaling pathway.Methods Thirty-five SPF male SD rats were used.Eight served as the blank control group.The remaining 27 were used to establish the MN model via a single tail vein injection of sheep anti-rat Fx1A serum.After successful model confirmation,these rats were randomly divided into three groups(n=9 each):the MN model group,the benazepril hydrochloride group[10 mg/(kg·/d)],and the GTW group(6.25 mg/kg/d).All groups received daily intragastric administration for 6 weeks.We collected 24-hour urine to mea-sure total urinary protein(24h-UTP).Blood samples from the abdominal aorta were analyzed for serum albumin(ALB),aspartate ami-notransferase(AST),alanine aminotransferase(ALT),urea nitrogen(BUN),creatinine(Cr),total cholesterol(TC),and triglyceride(TG).Renal histopathology was assessed by hematoxylin-eosin(HE)and periodic acid-Schiff methenamine(PASM)staining.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in renal tissues were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA and protein expression levels of AHR,NF-κB p65,COX-2,and Nrf2 in renal tissues were determined by RT-PCR and Western blot(WB),respectively.Results Compared with the model group,GTW treatment significantly decreased 24h-UTP,serum BUN,Cr,TC,TG,and renal MDA content(all P<0.01),while it increased serum ALB and renal SOD activity(P<0.01).GTW also ameliorated renal histopathological damage.Furthermore,GTW downregulated the mRNA and protein expression of AHR,NF-κB p65,and COX-2,and upregulated Nrf2 expression in renal tissues(all P<0.01).Conclusion GTW likely exerts its renoprotective effects in MN by inhibiting the AHR signaling pathway,which subsequently attenuates inflammatory response and oxida-tive stress,leading to reduced proteinuria,improved renal function,and delayed disease progression.