| Background and objectiveDiabetic nephropathy (DN) is the most common and serious microvascularcomplication of diabetes mellitus. As the prevalence of diabetes has increased year byyear, the end-stage renal disease caused by DN has been endangering the lives ofpatients with diabetes. In the last few years, immune response and inflammation hasbeen known are part of the mechanisms which cause kidney injury in diabetes. Andcurrent evidence supports a critical role for tubular epithelial-mesenchymal transitionin the evolution of diabetic complications. Therefore, inhibition of immune responseand inflammation, especially blockade of tubular epithelial-mesenchymal transitionmay become a good therapeutic approach for preventing the development of diabetescomplications including DN. Total glucosides of paeony (TGP) was the traditionalChinese herbal medicine in our country, its pharmacological effect isanti-inflammation, antioxidant and regulation of the immune. Our previous studiesshowed that the TGP can significantly reduce the urinary albumin excretion ofdiabetic rats, inhibite renal tissue extracellular matrix (extracellular matrix ECM)proteins type IV collagen production, suggesting that TGP have a significantrenoprotective effect.In the present study, we investigate the effect of totalglucosides of paeony (TGP) on renal tubulointerstitium cells transdifferentiation indiabetic rats and explore its possible renoprotection mechanisms.MethodsDiabetes was induced by injection of streptozotocin in rats. Rats was randomlydivided into three groups: control group, model group, model group treated with TGP. TGP50,100,200mg·kg-1·d-1was orally administered once a day for8wk. BG weredetermined according to standard methods.Urinary albumin excretion rate wasmeasured by enzyme immunoassay (EIA).Tubulointerstitial morphological analysiswas performed in PAS stained section. Expressions of E-cadherin (E-cad), a-smoothmuscle actin (a-SMA) and and vimentin (Vim) in renal tubulointerstitium weredetermined by immunohistochemistry method.Results1.Rats in each group general indicator of changes Compared with the controlgroup, model group rats showed as a blood glucose increased, weight loss, relativekidney weight (kidney weight/body weight) increased. TGP (50，100and200mg·kg-1·d-1) administration of8weeks did not prevent elevated blood glucose andweight loss of the model group. TGP (50，100and200mg·kg-1·d-1) administered ratsrelative kidney weight and the model group compared to decline, but the differencewas not statistically significant. Elevated24hours urinary albumin excretion rate wasmarkedly attenuated by TGP treatment with50，100and200mg·kg-1·d-1in diabeticrats．2.Rats in each group tubulointerstitial pathological changes The increasedindices for tubulointerstitial injury of model group were significantly higher than thatof the control group (P <0.01). The increased indices for tubulointerstitial injury ofTGP50mg·kg1.d1administered rats declined compared with the model group, butthe difference was not statistically significant. The increased indices fortubulointerstitial injury of TGP100,200mg·kg-1·d-1administered rats weresignificantly lower than model group (P <0.05, P <0.01).3.E-cad, a-SMA and Vim immunohistochemical staining in renal tissue Inrenal tubulointerstitium in diaetic rats, decreased expression of E-cad protein wassignificantly inhibited by TGP treatment with50100and200mg·kg-1·d-1(P<0.01)and elevated expression of a-SMA and Vim protein was also significantly inhibited byTGP treatment with50，100and200mg·kg-1·d-1(P<0.01). ConclusionsTGP can down-regulate the expression of a-SMA and Vim, and up-regulate theexpression of E-cad in diabetic renal tubulointerstitium cells and significantlyameliorates the pathological damage of the kidney of diabetic rats. Its mechanismmay be related to restrain the process of tubulointerstitium cells transdifferentiationin diabetic rats. |
PDF Full Text Request