The Role Of Toll Like Receptor4 On Pathogenesy Of Diabetic Nephropathy And The Effect Of Losartan On The Expression Of It In Kidney

Objective To investigate the changes of Toll-like receptor4(TLR4) expression in renal tissue and regulating possible mechanism in rats with diabetic nephropathy. Methods Male SD rats were randomly divided into two groups as follows: control group and model group . Model group were induced to be diabetic nephropathy by intraperitoneal injection with streptozoticin(STZ). 24h urine protein, creatinine, urea nitrogen, profile of kidney hypertrophy(KW/BW), urine albumen/ creatinine value(A/C), the plasma concentration of CRP and TNF-αwere determined at week 2, 4, 6, 8 and 12 respectively. The transmutation of renal pathomorphology was observed and the hyperplastic degree of extracellular matrix was evaluated. mRNA expression of TLR4 were detected by reverse transcript(RT) -PCR. Renal protein expression of TLR4, nuclear factor-кB( NF-кB), transforming growth factor-β1 (TGF-β1) and fibronectin (FN) were detected by immunohistochemical method.Results 24 hours urine protein excretion was increased, mng symptom of renal disease, at 2 week in model group. At same time, the TLR4 expression in renal tissue was markedly increased compared with control group. To follow the aggravation of the disease, the expression of TLR4 was durative increased. At 12 week, the plasma concentration of CRP and TNF-αof the rats which with diabetic nephropathy were raised up obviously and it emerged nephridial tissue fibrosis and injury of renal function .Positive correlation is found between TLR4 expression and nephridial tissue fibrosis, the same correlation also existed between TLR4 expression and injury degree of renal function.Conclusion TLR4 possibly via adjustment inflammatory reaction to play a pivotal role in the pathogenesis of renal damage in diabetic nephropathy. Objective To observe the inflammation depressant effect of losartan on experimental diabetic nephropathy in rat.Methods SD rats were randomly divided into three groups: control group, model group, losartan-treatment group. The latter two groups were induced to be diabetic nephropathy by intraperitoneal injection with 65 mg/kg streptozoticin(STZ). Then, 20 mg·kg-1·d-1 losartan was continuously given 1 week after STZ injection in losartan-treatment group. The 24h urine protein, urine albumen/ creatinine value (A/C), plasma concentration of CRP and TNF-αwere detected at week 4, 8 and 12 respectively. Renal protein expression of TLR4 and NF-кB were detected by immunohistochemical method. TLR4 mRNA expression in the renal was detected by reverse transcript (RT)–PCR. All of these were detected in losartan-treatment group at week 12.Results The 24h urine protein,A/C,plasma concentration of CRP and TNF-α,the renal expression of TLR4 and NF-кB increased in diabetic rats, compared with control group. Furthermore, TLR4 expression has positive correlation with NF-кB expression, 24h urine protein, A/C, plasma concentration of CRP and TNF-α. The plasma concentration of creatinine , CRP and TNF-αdecreased in losartan-treatment group , and the renal expression of TLR4 and NF-кB were also down-regulated (P<0.05).Conclusions Losartan can lessen the diabetic nephropathy impairment through down-regulation of the TLR4 and NF-кB expression in renal, reduction of CRP and TNF-αplasma concentration.