Terpinen-4-ol regulates SIRT1 /Nrf2 signaling to inhibit vascular oxidative stress injury in chronic kidney disease / 安徽医科大学学报

ABSTRACT

Objective @# To investigate the effect and signaling mechanism of terpinen-4-ol (T4O) on vascular oxida- tive stress injury in mice with chronic kidney disease ( CKD) ．@*Methods @# A CKD mice model was prepared using high phosphorus diet combined with adenine，and the normal group was given an equal volume of saline gavage．The CKD model with low expression of SIRT1 in vivo was established by tail vein injection of lentiviral SIRT1 RNAi for the study of signaling mechanism．The administration groups were given T4O at low and high doses ( 10 mg / kg and 20 mg / kg) for 6 weeks by continuous gavage．Serum was collected to detect urea nitrogen ( BUN) and creatinine ( CRE) levels，and HE staining was used to observe the morphology of blood vessels in the thoracic aorta of mice expression. @*Results @# T4O reduced serum BUN and CRE levels in CKD mice to improve renal function，improved kidney and thoracic aortic vascular morphology，reduced vascular tissue MDA content，increased SOD content，and reduced ROS levels ; T4O intervention promoted Nrf2 nuclear translocation and upregulated HO-1，NQO-1 and SIRT1 protein expression ; LV-SIRT1 RNAi + T4O group was able to inhibit the effect of T4O on CKD-induced MDA and SOD levels，partially counteracting the effect of T4O in upregulating Nrf2 nuclear translocation and the protein expression levels of SIRT1，HO-1 and NQO-1．@*Conclusion @#T4O has a protective effect against oxidative stress in- jury in the thoracic aorta of CKD mice，and its molecular signaling mechanism may be related to the level of drug- regulated SIRT1 / Nrf2 cascade signaling.