菊苣酸通过调控Nrf2/HO-1对糖尿病肾病氧化应激的抑制作用

Cichoric acid inhibits oxidative stress in diabetes nephropathy by regulating Nrf2/HO-1

目的探索菊苣酸(CA)对糖尿病肾病(DN)小鼠氧化应激的作用及其可能机制。方法给予C57BL/6小鼠高脂饮食,同时注射链脲霉素建立DN小鼠模型,并使用20 mmol/L的D-葡萄糖刺激NRK-52E细胞建立体外模型。ELISA检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)水平。对肾组织进行HE染色、Masson染色和PAS染色,Western blot检测Nrf2和HO-1蛋白水平。结果CA能减少肾重指数,改善肾小球结构损伤,改善摄取水量、尿蛋白水平、血清肌酐和尿素氮水平。在DN小鼠模型和体外模型中,CA均能降低肾组织和细胞中的MDA水平,增加SOD、GSH和GSH-PX水平。CA还激活DN小鼠肾脏组织和体外模型肾细胞中的Nrf2/HO-1信号通路。结论CA通过激活Nrf2/HO-1信号通路,减少DN及其氧化应激损伤。CA可能是一种治疗或预防DN的有希望的治疗药物。

Objective To investigate the effect of cichoric acid(CA)on diabetes nephropathy(DN)and the molecular mechanism of reactive oxygen species(ROS)oxidative stress.Methods We fed C57BL/6 mice a high-fat diet and injected streptozotocin to establish a DN model.In addition,we stimulated NRK-52E cells with 20 mmol/L D-glucose to establish a DN model in vitro.C57BL/6 mice were fed with high-fat diet and injected with streptozotocin to establish DN model.NRK-52E cells were stimulated with 20 mmol/L D-glucose to establish DN model in vitro.ELISA was used to measure the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and glutathione peroxidase(GSH-PX).Renal tissues were stained with HE,Masson and PAS,and Western blot was used to detect Nrf2 and HO-1 protein levels.Results CA reduced index of kidney weight,improved glomerular structural damage,improved water intake,urine protein levels,serum creatinine,and urea nitrogen levels.In the mouse model of diabetes nephropathy,cichoric acid inhibited the level of MDA in renal tissue and increased the levels of SOD,GSH and GSH-PX.Meanwhile,in the in vitro model,chicory acid inhibited MDA levels in renal cells and increased SOD,GSH and GSH-PX levels.Finally,cichoric acid promoted Nrf2/HO-1 signaling pathway in kidney tissue of diabetes nephropathy mice and also activated Nrf2/HO-1 signaling pathway in kidney cells in vitro.Conclusion Cichoric acid reduces oxidative stress damage in DN by activating Nrf2/HO-1 signaling pathway.Cichoric acid may be a promising therapeutic drug for treating or preventing diabetes nephropathy.