The Mechanism Of Triptolide Influence The ADR-induced Podocyte Apoptosis

Objective:To assess the influnce of triptolide on the apoptosis of podocytes in adriamycin nephropathy(ADR)rats and to explore potential mechanisms.Methods :wistar clear rats were randomly divided into three groups:normal control group(N group),adriamycin-induced nephropathy group(ADR group)and triptolide-treat ed ADR group(T group).The ADR group and T group were injected with adriamycin(6.5mg/kg)via tail-vein for one time.while the N group were injected normal salinevia with th e same volume via tail-vein for one time.Observe 24 h hour urinary protein count in 2?4?6?8weeks,Then the rats were sacrificed on week 8 and measured the biochemical para meters,Observed the pathological changes of the kidney by light microscope and electro n microscope,counted the apoptosis of pcodcytes of rats using TUNEL method.Determi ned WT-1 by immunohistochemistry,Detected the m RNA of Synaptopodin?p53?Notc h 1 by RT-PCR.Besides,detected Synaptopodin?Notch 1?Hes 1 by Western blotting.Results :(1).Compared with the N group,the level of 24 h urinary protein?BUN?SCr ?Cys C of ADR rats were significantly increased(P<0.05),The density of podocytes was reduced(P<0.05),mesangial region becomes wider and mesangial hyperplasia obviously increased,but 24 h urinary protein ? SCr ? Cys C were decreased in T group(P<0.05)and he density of podocytes were increased(P<0.05),the changes of the kidney were improved.(2).Synaptopodin m RNA and protein expression were markedly decreased,p53 m RNA expression were increased in ADR group(P<0.05),while the volume of kidney is bigger than Ngroup,apoptotic podocytes by TUNEL increased(P<0.05).However,higher Synaptopodin m RNA and protein expression improved,p53 m RNA expression were decreased,less apoptotic podocytes were found in T group(P<0.05).(3).Compared with N group,the m RNA and protein expression of Notch1 and HES1 were higner in ADR group(P<0.05),as for the Tgroup,the expression of Notch1 and HES1 were decreased(P<0.05).Conclusion:1.we found the ADR rats podocytes damage and apoptosis,through the relevant testing,we found that podocytes apoptosis increased and the expression of Notch1?Hes1?p53 as same.While the expression of podocytes marker protein Synaptopodin reduced.2.Notch pathway activated target genes His then regulated p53 induced podocytes apoptosis.3.After triptolide-treated we found the apotosis of podocytes and the expression of Notch pathway decreased.Therefore,we thought the ADR rats podocytes apoptosis may related to the Notch pathway activation,and triptolide may ameliorate the ADR-induced podocyte apotosis whose mechanism may be contribute to suppression of Notch signaling pathway.