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

摘要:

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。

Abstract:

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.