Effects Of Total Glucosides Of Paeony On TLR2,4Expresion In The Kidney Macrophages From Diabetic Rats

[Background]: Diabetic nephropathy (DN) is chronic renal damage due to long-termglucose metabolic abnormalities, which are involved in the pathophysiological process ofmultiple factors. Recently studies reported inflammation induced by macrophage has veryclose relationship with the incidence of DN. Therefore, inhibition of immune responseand inflammation, especially block the function of macrophage may become a keytherapeutic strategy for preventing the development of diabetes complications.Toll-like-receptors (TLR) activate the inflammatory response, TLRs/NF-κB signalpathway plays a very important role in the development of DN. Studies show that TLRsmay be involved in mediating the occurrence of DN. At present, the research shows thatpharmacological effect of TGP is anti-inflammation, antioxidant and regulation of theimmune, but the main mechanism of action is still not clear. Our previous study showedthat TGP had obvious protective effect on diabetic rat kidney, and still has relationshipwith the active of restraint renal tissue NF-κB. In the present study, we investigate TGP onthe effect of expression of TLR2, TLR4and NF-κB-p-p65in the kidney macrophages ofdiabetic rat.[Objective]：To investigate the effect of total glucosides of paeony on TLR2and TLR4expresion in the kidney macrophages from diabetic rats.[Methods]：Diabetic rats were induced with streptozotocin. Rats were separated intothree groups at random: control group, model group, model group treated with TGP.TGP50,100,200mg·kg-1·d-1was orally administered once a day for8weeks.Relative kidney weight (RKW) and24hour urinary albumin excretion rate (AER) weremeasured. Kidney pathology was observed by light microscopy. ED-1+, ED-1+TLR2+,ED-1+TLR4+and NF-κB-p-p65+cells were measured with immunohistochemistry anddouble immunohistochemistry.[Results]：There was a significant increase about blood glucose and body weight inmodel group compared with the control (P<0.01). TGP could not prevent its increase.Elevated24h urinary albumin excretion was markedly attenuated by TGP treatmentwith50,100and200mg·kg1in diabetic rats. Elevated glomerular volume wassignificantly attenuated by TGP treatment with50,100and200mg·kg-1(P<0.05), andincreased TII were only ameliorated by TGP treatment with100and200mg·kg-1(P<0.01). There were marked accumulation of ED-1+, ED-1+TLR2cells, ED-1+TLR4cells and NF-κB-p-p65+cells were significantly elevated in the kidneys from diabeticgroup, while they were significantly inhibited by TGP treatment.[Conclusion]：TGP could ameliorate early renal injury and its mechanism may be atleast partly correlated with the suppression of increased TLR2and TLR4expression inmacrophages from diabetic rat kidney.