In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic（db/db） mice received everolimus（2 mg/kg every day） or rapamycin（2 mg/kg every day） f...In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic（db/db） mice received everolimus（2 mg/kg every day） or rapamycin（2 mg/kg every day） for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1（TGF-β1）and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal tissue as well as in mesengial cell culture samples.Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy,and in decreasing accumulation and expansion of the extracellular matrix.However,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorption rate.展开更多
文摘In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic（db/db） mice received everolimus（2 mg/kg every day） or rapamycin（2 mg/kg every day） for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1（TGF-β1）and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal tissue as well as in mesengial cell culture samples.Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy,and in decreasing accumulation and expansion of the extracellular matrix.However,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorption rate.
文摘目的研究红景天苷(Salidroside,Sal)对糖尿病肾病(Diabetic nephropathy,DN)的保护作用及其作用机制。方法通过测定血浆脂质、β2-微球蛋白、血浆肌酐、血液尿素氮水平以及肾脏组织HE染色检测Sal对小鼠肾脏的保护作用。MTT法检测高级糖基终产物(Advaned glycation end product,AGE)对HK-2细胞活性的影响。免疫蛋白印记法检测Sal对AGE诱导的HK-2细胞中凋亡相关蛋白Bax、Bcl-2、细胞核因子2相关因子2(Nrf2)、TGF-β1以及胶原蛋白Ⅰ的蛋白表达,caspase-3和caspase-9试剂盒检测其活性。结果Sal能够降低DN模型体内血浆脂质、β2-微球蛋白、血浆肌酐和血液尿素氮水平。Sal能够减轻糖尿病对肾脏组织的损伤。Sal能够逆转由AGE诱导的HK-2细胞活性降低。Sal能够上调由AGE导致的Nrf2蛋白表达下调;TGF-β1以及胶原蛋白Ⅰ表达上调,Bax以及Bcl-2比例下降,caspase-3、caspase-9活性降低。结论Sal通过调控Nrf2的表达逆转由AGE引起的HK-2细胞凋亡以及糖尿病导致的肾脏组织损伤,进而对抗DN,产生类似二甲双胍(Metformin,MET)的作用。Sal可成为DN的潜在治疗药物。
