mTtor通路在糖尿病肾病大鼠足细胞损伤中的作用

摘要

Objective To observe effects of mTOR blocker on podocyte protein in diabetic nephropathy ( DN) rats, and to investigate the potential mechanism of DN podocyte injury .Methods Normal rats as control group ( A group).The DN rat models were induced with STZ method , and randomly divided into DN group ( B group), DN +FK506 group (C group) and DN+ku0063794 group (D group).FK506 and ku0063794 were given to rats in C group and D group, respectively.The blood glucose, creatinine clearance rate (Ccr), 24-hour proteinruia, mTOR, Raptor, Ric-tor, Ezrin and α-SMA protein at the 0, 4 and 8 weeks were measured .Results The 24-hour proteinruia in B groups were significantly higher than A group ( P<0.05 ) .The Ccr in B groups were significantly lower than A group ( P<0.05).The mTOR in B groups were significantly higher than A group (P<0.05), while it was significantly lower in C、D groups than B group (P<0.05).Raptor and Rictor proteins in B groups were significantly higher than A group (P<0.05), while they were significantly lower in C、D groups than B group (P<0.05).Ezrin in B groups were significantly lower than A group (P<0.05), while it was significantly higher in C、D groups than B group (P<0.05).α-SMA in B group was significantly higher than A group (P<0.05), while it was significantly lower in C、 D groups than B group (P<0.05).Pathological scores in C、 D groups were significantly reduced when compared with B group (P<0.05). Rictor was significantly positively correlated with α-SMA and negatively correlated with Ezrin .However , there was no significant correlation between Raptor and Ezrin or α-SMA.Conclusion The mTORC2 pathways may participate in the expression of podocyte Ezrin and α-SMA proteins in DN , and FK506 may also block mTORC2 signaling pathways .%目的 观察mTOR阻断剂对糖尿病肾病(DN)大鼠足细胞蛋白的影响,探讨mTOR通路在DN足细胞损伤中的可能机制.方法 以正常大鼠作为对照组(A组);STZ造模,模型组随机分为DN组(B组)、DN+FK506干预组(C组)、DN+ku0063794干预组(D组).C、D组分别予FK506、ku0063794灌胃.灌胃前1 d、灌胃4、8周分别检测各组大鼠血糖、内生肌酐清除率(Ccr)、24 h尿蛋白;4、8周时检测肾组织mTOR、Raptor、Rictor、Ezrin、α-SMA的表达.结果 4周、8周时C、D组24 h尿蛋白低于B组(P<0.05);Ccr高于B组(P<0.05);mTOR、Raptor、Rictor在B组升高,C、D组均下降(P<0.05);B组Ezrin蛋白明显低于A组(P<0.05),C、D组表达上升(P<0.05);B组α-SMA蛋白高于A组(P<0.05),C、D组降低(P<0.05);病理评分C、D组均较B组降低(P<0.05).相关性分析中Rictor与α-SMA呈正相关(P<0.05),与Ezrin呈负相关(P<0.05);Raptor与Ezrin、α-SMA均无相关性.结论 阻断mTOR通路能降低DN大鼠的尿蛋白、升高Ccr、改善肾脏病理,对肾脏有保护作用;mTORC2信号通路可能参与了DN的足细胞的Ezrin、α-SMA蛋白的表达;FK506也可能阻断mTORC2通路.