Effect Of Total Glucosides Of Paeony On The Expressionof Txnip, Trx And ASK1 In The Kidney From Diabetic Rats

Background Diabetic nephropathy is one of common microvascular lesions of diabetes mellitus. Recently,the living standards is improving, diabetes patients increase gradually, make the diabetic nephropathy become one of “killers” that threaten human health.Many studies have investigated that oxidative stress involved in the occurrence and development of diabetic nephropathy.Thioredoxin(Trx) system is a kind of system which can against oxidative stress and maintain the balance of oxidation-reduction reaction, moreover the reduced Trx can inhibits ASK1 activation and promotes the ASK1-induced apoptosis.The thioredoxin interacting protein(Txnip), which for the Trx function and expression of negative regulation factors, can reduce the expression of Trx and increase oxidative stress.Our prior researches considered that total glucosides of paeony(TGP) can protect diabetic nephropathy obviously with its function of resistance to oxidative stress, but the regulating role of TGP in Trx system is unclear,this experiment can research the effect of TGP on the expression of Txnip, Trx and apoptosis signal kinase 1(ASK1) in diabetic rat kidney tissue and provide an experimental basis for clinical therapy for diabetic nephropathy with TGP.Methods. Diabetes Rats induced with streptozotocin were randomly divided in to model group and model group treated with TGP(50,100,200 mg/kg?d),for 8 week),besides,use normal rats as control group.We measured 24 h urinary albumi n excretion rate(UAER) with ELISA.Txnip,Trx and ASK1 were determined with immunohischemistry, Western blot and real-time PCR.Result Elevated 24 h urinary albumin excretion rate was obviously decreased in TGP treatment with 50,100,200 mg/kg?d. Compared with control group, analysis of the immunohischemistry showed the expression of Txnip and ASK1 was markly increased,and the expression of Trx was decreased(P<0.01).TGP treatment with 50,100,200 mg/kg?d could obviously reduce the expression of Txnip and ASK1(P<0.01,P<0.05),and increased the expression of Trx(P<0.01,P<0.05),Western blot showed that the obviously increased expression of Txnip and ASK1 in the renal of model group was significantly suppressed by TGP treatment(P<0.05).Real-time PCR analysis showed that Txnip m RNA expression in model group was significantly higher than control group(P<0.01), and Trx m RNA expression was opposite(P<0.01),the expression of Txnip m RNA in TGP treatment with 50,100,200 mg/kg?d was significantly decreased(P<0.05),and that of Trx m RNA was increased(P<0.05).Conclusion There is an abnormity occuring in the thioredoxin system in the renal tissue of diabetic nephropathy rats,TGP obviously has the function of renal protection,and its mechanism may be related to the inhibition of Txnip expression and the enhancement of Trx expression.