Study Of Regulation Of Total Glucosides Of Paeony On TLR2,4/NF-κB Signal Pathway In The Kidney From Diabetic Rats

Background and objective Diabetic nephropathy is a major cause of end-stage renaldisease. There are no special treatments, hence, preventing its happening anddevelopment is extremely important. In the last few years, activation of immuneresponse and inflammation has been known part of the mechanisms which cause kidneyinjury in diabetes. NF-κB is a role of core in diabetic nephropathy and has beenconsidered as a central adjustment factor in diabetic vascular lesions. TLRs initiate theinflammatory response, TLRs/NF-κB signal pathway plays an important role in thediabetic nephropathy development. Total glucosides of paeony (TGP) has curativeeffects in clinical trial in the treatment of rheumatoid arthritis, hepatitis, senile disease.Our previous study show that TGP has obvious protective effect on diabeticnephropathy. In the present study, we further investigate the regulation of TGP on TLR2,TLR4and NF-κB-p-p65activation in the kidney from diabetic rats and explore itspossible renoprotection mechanisms.Methods Fifty adult male Sprague-Dawley rats were separated into five groups atrandom. Control group (n=10), model group (n=10), model group treated with TGP (50mg·kg1d1, n=10), model group treated with (TGP100mg·kg1d1, n=10) and modelgroup treated with TGP (200mg·kg1d1, n=10). Diabetes was induced withstreptozotocin (65mg·kg1d1) in rats, and TGP was orally administered once a day for8wk to rats. Eight weeks after STZ injection, the following determinations were done insamples:1.BG were determined according to standard methods;2.Urinary albuminexcretion rate was measured by enzyme immunoassay (EIA);3.TLR2, TLR4and NF-κB-p-p65positive expression were measured with immunohistochemistry in thekidney.Results Elevated24h urinary albumin excretion was markedly attenuated by TGPtreatment with50,100and200mg·kg1in diabetic rats. Analysis of the immunost-aining showed the expression of TLR2, TLR4and NF-κB-p-p65in diabetic rats wassignificantly increased compared with control rats in the kidney（P<0.01）．TGPtreatment with50,100and200mg·kg1could markedly reduce TLR2expression in thetubulointerstitium（P<0.01）, TLR4and NF-κB-p-p65expression in the glomeruli andtubulointerstitium could all been markedly reduced（P<0.05，0.01）.Conclusion Our data suggest that TGP treatment ameliorates early renal injury via theinhibition of the overexpression of TLR2,4/NF-κB signal pathyway in the kidney fromdiabetic rats．...