【摘要】 目的:探讨C肽对链脲佐菌素诱导的糖尿病肾病大鼠肾小管间质氧化应激的影响。方法:腹腔注射链脲佐菌素的Wistar大鼠发展至糖尿病肾病后,随机分为对照组、C肽组,经腹腔埋入微渗泵用药。以同龄正常Wistar大鼠为正常组。用药前及用药后每4周检测各组大鼠血糖及24 h尿白蛋白。用药12周后,免疫组织化学染色观察大鼠肾小管间质转化生长因子β1(TGF-β1)表达;新鲜肾小管间质组织匀浆WST-1法检测超氧化物歧化酶(SOD)活性,TBA法检测丙二醛(MDA)含量,Real-time PCR检测蛋白激酶A m RNA的表达。结果:与正常组对比,对照组大鼠血糖及24 h尿白蛋白升高,肾小管间质TGF-β1表达增加、SOD活性降低、MDA含量升高、蛋白激酶A m RNA表达下调;经C肽干预后,大鼠血糖无明显变化,24 h尿白蛋白升高减缓,肾小管间质TGF-β1表达减少、SOD活性升高、MDA含量降低、蛋白激酶A m RNA表达上调。结论:C肽通过激活蛋白激酶A途径减轻糖尿病肾病大鼠肾小管间质的氧化应激反应,改善肾小管间质纤维化,减轻蛋白尿。更多还原

【Abstract】 Objective To investigate the effect of C peptide on tubulointerstitial oxidative stress injury inrats with diabetic nephropathy(DN) induced by streptozotocin(STZ).Methods Wistar rats with DN induced bySTZ were randomly divided into control group and C peptide group.All rats were treated via intraperitoneal micro-osmotic pump.Normal Wistar rats at the same age were used as the normal group.Blood glucose and24 h urinaryalbumin were measured before treatment and every 4 weeks during treatment period.After 12 weeks of treatment,the expression of transforming growth factor-β1(TGF-β1) in renal tubulointerstitium was detected byimmunohistochemical staining.Fresh tubulointerstitial tissue homogenate was harvested and the activity ofsuperoxide dismutase(SOD) was detected in WST-1 method,the content of malondialdehyde(MDA) was detected inTBA method,and the expression of protein kinase A(PKA) m RNA was detected by Real-time PCR.Results Levels of blood glucose,24 h urinary albumin,MDA content and the expression of TGF-β1 were higher in thecontrol group than those in the normal group,while SOD activity decreased and PKA m RNA was downregulated.Cpeptide treatment did not change blood glucose level but slowed down the increasing of 24 h urinary albumin,reduced the tubulointerstitial TGF-β1 expression and MDA content,increased the SOD activity and upregulated thePKA m RNA expression.Conclusions C-peptide can decrease the tubulointerstitial oxidative stress in DN rats byactivating PKA pathway and then improve tubulointerstitial fibrosis and attenuate proteinuria.更多还原