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目的 探讨还原型谷胱甘肽(reduced glutathione,GSH)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠肾脏线粒体保护及机制.方法 STZ诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病非干预组(DM组)和GSH干预组(DM+GSH组),并以正常组(NC组)作对照.干预8周后,测定各组大鼠尿白蛋白排泄率(UAER)、血肌酐(SCr)、血尿素氮(BUN)水平,光镜观察肾脏组织形态学变化,检测血清和肾皮质中丙二醛(MDA)、超氧化物歧化酶(SOD)的含量以及各组肾脏线粒体膜电位和肿胀度的变化.结果 DM组大鼠UAER、SCr、BUN较NC组显著升高(均P＜0.05),肾脏组织发生糖尿病肾病病理改变,血清MDA(μmol/L)和肾皮质中MDA(μmol/g)显著升高(5.59±1.03 vs 2.97±0.77;4.80±0.83 vs 2.98±0.75;均P＜0.01),血清SOD(U/ml)和肾皮质中SOD(U/mg)含量显著降低(89.13±22.73 vs 124.1±9.27;46.05±10.24 vs 89.89±17.62;均P＜0.01),肾脏线粒体膜电位明显降低(495.79±124.71 vs 965.77±246.48,P＜0.05),线粒体肿胀度趋势明显减弱.与DM组相比,DM+GSH组大鼠UAER、SCr、BUN显著降低(均P＜0.05),肾脏病理形态得到一定改善.血清MDA(μmol/L)和肾皮质中MDA(μmol/g)降低(4.15±0.59 vs 5.59±1.03;3.39±0.61 vs 4.80±0.83;均P＜0.05),血清SOD(U/ml)及肾皮质中SOD(U/mg)升高(112.92±8.93 vs 89.13±22.73;83.15±16.75 vs 46.05±10.24;均P＜0.05),肾脏线粒体膜电位显著升高(715.97±188.65 vs 495.79±124.71,P＜0.05),线粒体肿胀度趋势增强.结论 还原型谷胱甘肽对STZ诱导的糖尿病大鼠肾脏病变有一定程度的保护作用,其机制可能与线粒体的功能改变有一定关系.

Objective To explore the renoprotective effect of reduced glutathione on streptozotocin-induced diabetic rats and its possible mitochondrial mechanism in the kidneys.Methods After the diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ),the diabetic rats were randomly divided into non-treated group (DM),and reduced glutathione-treated group (DM + GSH).The normal non-diabetic rats were served as the control group (NC).Eight weeks later,the excretion of urinary albumin excrection rate (UAER),serum creatinine (SCr) and serum urea nitrogen (BUN) were detected.Morphological changes of the kidney were observed by optics microscope.The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in serum and renal cortex were detected.Meanwhile,kidney mitochondrial membrane potential and mitochondrial swelling were measured between the different groups.Results Compared with the NC group,the excretion of UAER,SCr and BUN were significantly increased (all P ＜ 0.05),and pathological changes of diabetic nephropathy occured in the DM group.The levels of MDA in serum (μmol/L) and renal cortex (μmol/g) were significantly elevated (5.59±1.028 vs 2.97±0.77,4.80±0.83 vs 2.98±0.75,all P ＜ 0.01),and the activity of SOD in serum (U/ml) and renal cortex (U/mg) was significantly reduced in the DM group(89.13±22.73 vs 124.1±9.27,46.05±10.24 vs 89.89±17.62,all P ＜0.01).The kidney mitochondrial membrane potential was significantly decreased (495.79±124.71 vs 965.77±246.48,P ＜ 0.05),and mitochondrial swelling was weaken in the DM group.Compared with the DM group,the excretion of UAER,SCr and BUN were significantly decreased (all P ＜ 0.05),and above abnormal pathological changes were improved in the DM + GSH group.The levels of MDA in serum (μmoL/L) and renal cortex (μmol/g) were significantly reduced (4.15±0.59 vs 5.59±1.03,3.39±0.61 vs 4.80±0.83,all P＜0.05),and the activity of SOD in serum(U/ml) and renal cortex(U/mg) was significantly elevated in the DM + GSH group (112.92±8.93 vs 89.13±22.73,83.15±16.75 vs 46.05±10.24,all P＜0.05).The kidney mitochondrial membrane potential was significantly elevated (715.97±188.65 vs 495.79±124.71,P ＜ 0.05) and mitochondrial swelling was reinforced.Conclusion Reduced glutathione could ameliorate the function of mitochondria in the kidneys of STZ-induced diabetic rats to show nephroprotective effect.