香芹酚通过SIRT1/FOXO1通路减轻糖尿病肾病大鼠氧化应激损伤

Carvacrol alleviates oxidative stress damage in rats with diabetic nephropathy via the SIRT1/FOXO1 pathway

目的:研究香芹酚通过SIRT1/FOXO1通路减轻糖尿病肾病(diabetic nephropathy,DN)大鼠氧化损伤的机制。方法:采用高脂饮食和腹腔注射链脲佐菌素建立DN大鼠模型,将DN大鼠分为对照组、模型组、L-XQF组(5 mg/kg)、M-XQF组(10 mg/kg)和L-XQF组(20 mg/kg)。检测大鼠空腹血糖(fasting blood glucose,FBG)、尿素氮(urea nitrogen,BUN)、血肌酐(serum creatinine,SCr)、尿微量蛋白(urine microprotein,U-mAlb)的含量;之后处死大鼠,采集肾脏组织,HE染色和Masson染色分别观察大鼠肾脏组织病理变化和纤维化情况;ELISA法检测肾脏组织丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平;Western blot检测肾脏组织中SIRT1/FOXO1通路相关蛋白水平。结果:香芹酚能够降低DN大鼠FBG、BUN、SCr、U-mAlb和MDA水平,改善大鼠肾脏组织病理损伤及纤维化,增加SOD、GSH-Px含量及SIRT1、FOXO1蛋白水平。结论:香芹酚可能通过SIRT1/FOXO1通路抑制DN大鼠肾脏组织的氧化应激,从而减轻肾脏损伤及改善肾脏纤维化。

Objective:To investigate the mechanism of carvacrol alleviating oxidative stress damage in rats with diabetic nephropathy(DN)via the SIRT1/FOXO1 pathway.Methods:A rat model of DN was established by high-fat diet and intraperitoneal injection of streptozotocin,and then DN rats were divided into control group,model group,L-XQF group(5 mg/kg),M-XQF group(10 mg/kg),and L-XQF group(20 mg/kg).Fasting blood glucose(FBG),blood urea nitrogen(BUN),serum creatinine(SCr),and urinary microprotein(U-mAlb)were measured.After the rats were sacrificed and renal tissue samples were collected,HE staining and Masson staining were used to observe the pathological changes and fibrosis of renal tissue;ELISA was used to measure the levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in renal tissue;Western blot was used to measure the expression levels of SIRT1/FOXO1 pathway-related proteins.Results:Carvacrol reduced the levels of FBG,BUN,SCr,U-mAlb,and MDA,improved the pathological injury and fibrosis of renal tissue,and increased the content of SOD and GSH-Px and the levels of SIRT1 and FOXO1 proteins.Conclusion:Carvacrol may inhibit oxidative stress in renal tissue of DN rats via the SIRT1/FOXO1 pathway,thereby alleviating renal injury and improving renal fibrosis.