硒蛋白Se-76P对STZ诱导的小鼠糖尿病肾病模型肾功能及生化指标的影响

Effect of selenium Se-76P on STZ-induced renal function and biochemical indexes in mice with diabetic nephropathy

研究含硒蛋白(Se-76P)对链脲佐菌素(STZ)诱导的小鼠糖尿病肾病的保护作用。C57BL/6J雄性小鼠腹腔注射STZ(40 mg/kg)制备糖尿病肾病模型,将60只小鼠分为六组,正常对照组(Ⅰ组)、糖尿病肾病模型组(Ⅱ组)、模型+Se-76P低剂量组(Ⅲ组)、模型+Se-76P中剂量组(Ⅳ组)、模型+Se-76P高剂量组(Ⅴ组)和模型+胰岛素治疗组(Ⅵ组)。各组小鼠均采用皮下注射方式给药,Ⅰ组和Ⅱ组给予生理盐水;Ⅲ、Ⅳ、Ⅴ组分别给予低(20μmol/kg)、中(40μmol/kg)、高(60μmol/kg)浓度Se-76P蛋白;Ⅵ组给予5 U/kg·d胰岛素。各组连续给药4周,每周测量小鼠体重;实验结束后检测各组小鼠空腹血糖、血清肌酐(SCr)和尿素氮(BUN)水平;检测各组小鼠尿肌酐(UCr)和尿微量白蛋白(MAU)水平,并计算肌酐清除率(CCr);检测肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)水平。与模型组相比,Se-76P各治疗组空腹血糖值均降低;SCr、BUN、UCr、MAU水平以及CCr均显著降低(p<0.01或0.05);肾组织中MDA水平明显降低(p<0.01),而SOD和GPx活性明显升高(p<0.01或0.05)。Se-76P可能通过提高SOD和GPx活性,提升抗氧化水平,改善STZ诱导的糖尿病肾病小鼠模型的肾功能。

To explore the role and mechanism of selenium protein（ Se-76P） on streptozocin-induced diabeticnephropathy in mice.Diabetic nephropathy model were prepared with streptozocin（ 40 mg/kg） by intraperitoneal injection in male C57BL/6J male mice.60 mice were divided into six groups,normal control group（ group Ⅰ）,model of diabetic nephropathy group（ groupⅡ）,model ＋ low-dose Se-76 P group（ group Ⅲ）,model ＋ middle-dose Se-76 P group（ group Ⅳ）,model ＋ high dose Se-76 P group（ group Ⅴ） and insulin treatment group（ group Ⅵ）. Both groups of mice were administrated by subcutaneous injection way,group Ⅰ and group Ⅱ was given saline,group Ⅲ,Ⅳ and Ⅴ were given low（ 20 μmol/kg）,middle（ 40 μmol/kg） and high（ 60 μmol/kg） concentration of Se-76 P protein,group Ⅵ was given insulin,5 U/kg·d. All groups were treated for 4weeks,and body weights were measured every week. After the experiment,blood glucose,serum creatinine（ SCr） and urea nitrogen（ BUN） levels were measured in serum. The urine creatinine（ UCr） and microalbuminuria（ MAU） levels were detected and the creatinine clearance（ CCr） was calculated,renal tissue malondialdehyde（ MDA）,superoxide dismutase（ SOD） and glutathione peroxidase（ GPx） levels were also detected.Compared with model group,fasting blood sugar were decreased in Se-76 P administrated groups,the levels of SCr,BUN,UCr,MAU and CCr were significantly decreased（ p〈0.01 or 0.05）.The MDA level was decreased in kidney tissues significantly（ p〈0.01）,SOD and GPx activity were increased significantly（ p〈0.01 or p〈0.05）. Se-76 P may improve renal function in STZ-induced diabetic nephropathy mice by increasing SOD and GPx activities,enhancing antioxidant levels.