肌肽对糖尿病肾病大鼠氧化应激及NF-κB信号通路的影响

Effects of carnosine on oxidative stress and NF-κB signaling pathway in rats with diabetic nephropathy

目的探讨肌肽对糖尿病肾病(DN)大鼠肾组织的保护作用及其对氧化应激、NF-κB信号通路的影响。方法60只SPF级8周龄雄性SD大鼠,随机选取12只为对照组,其余予以高糖高脂饮食+链脲佐菌素腹腔注射建立糖尿病模型。注射链脲佐菌素3 d后,将符合糖尿病标准大鼠随机分为模型组、肌肽(100、300、900 mg/kg)组。肌肽各组分别灌胃100、300、900 mg/kg肌肽,每日1次。8周后,检测空腹血糖(FBG)、血清肌酐(Scr)、尿素氮(BUN)、24 h尿微量白蛋白(mAlb)。PAS染色法观察大鼠肾形态学变化;试剂盒检测肾组织的超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)含量;免疫组织化学及Western blot检测肾组织P-NF-κB P65蛋白的表达。结果DN大鼠建模成功。与模型组相比,肌肽组肾组织病理损伤明显减轻。肌肽各组大鼠mAlb、FBG、BUN水平下降,呈量-效依赖性关系(P<0.05),而SOD、GSH、GSH-Px的含量逐级升高,同时MDA和P-NF-κB P65含量减少。结论肌肽对DN模型大鼠肾组织具有保护作用,其机制可能与抑制氧化应激和NF-κB信号通路异常激活有关。

Objective To investigate the protective effects of carnosine(CAR)on diabetic nephropathy(DN)in rats and its effects on oxidative stress and NF-κB signaling pathway.Methods Sixty SD male rats of 8-week-old,except the normal group(n=12),were given high fat and sugar diet,and intraperitoneal injection of STZ to establish diabetes rats model.Three days after the injection of STZ,the rats that conform to pre-determined criterion were randomly divided into a diabetic nephropathy group and a carnosine(100,300,900 mg/kg)group.The carnosine groups were intragastrically administered with 100,300,and 900 mg/kg carnosine once a day.After 8 weeks of carnosine administration,fasting blood glucose(FBG),serum creatinine(Scr),blood ureanitrogen(BUN),and 24-hour micro albumin(mAlb)were measured.Morphological changes of rat kidney were observed by PAS staining.The activity of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and the content of malondialdehyde(MDA),glutathione(GSH)in the nephropathy were detected by respective commercial kits.Renal tissue phosphate NF-κB P65 protein expression were detected by immunochemistry and Western blot.Results The carnosine can effectively alleviate the pathological damage of kidney tissue.Compared with the diabetic nephropathy group,carnosine could decrease the levels of 24 h urine protein,FBG,Scr and BUN,with a dose-effect manner(P<0.05).Carnosine also could increase the contents of SOD,MDA,GSH,GSH-Px and decrease phosphate NF-κB P65,and the content of MDA in kindey.Conclusions Carnosine had a protective effect on rats of DN model,and its protective mechanism may relate to the inhibition of oxidative stress and NF-κB signaling pathway.