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Objective To observe the the TOLL receptor 4 (Toll-like receptor4 TLR4) expression changes in rat kidney tissue of diabetic nephropathy (diabetic nephropathy DN), a preliminary study and the possible role of TLR4 in DN development occurs. Method test divided into two groups - the model group and made group. The diabetic model of the one-time high-dose the model rats applications intraperitoneal injection of streptozotocin (streptozoticin STZ) solution, only to manipulate the group given intraperitoneal injection of STZ-free solution. Model group in successful modeling 2w, 4w, 6w, 8w, 12w were determined and made group 24h urinary protein excretion, serum creatinine (Cr), blood urea nitrogen (BUN), kidney weight / body weight (KW / BW) urinary albumin / creatinine ratio (A / C), serum CRP and TNF-α titer; morphological changes in the kidney injury and measuring the degree of proliferation of extracellular matrix; RT-PCR assay in renal tissue of TLR4 mRNA expression; immune group of renal tissue was detected TLR4, nuclear factor кB (NF-кB), transforming growth factor-β1 (transforming growth factor-β1 of TGF-β1), fibronectin (fibronectin FN), protein expression. Diabetic rats 2w soon as 24h urinary protein excretion increases early signs of kidney disease, the renal tissue of TLR4 and NF-кB expression began to increase, compared with the control group, the difference was significant, and with the severity of aggravation was continuing to increase. 12w serum titer was significantly higher test rats inflammatory mediators, and the emergence of renal fibrosis and renal injury. Correlation analysis showed that the expression of TLR4 inflammatory reaction, the degree of renal fibrosis and renal function degree of injury showed a significant positive correlation. Conclusion TLR4 signal pathway may be through the activation of immune and inflammatory response involved in the occurrence and development of diabetic nephropathy. Objective To investigate losartan inhibition of inflammation in diabetic nephropathy. The intraperitoneal injection of streptozotocin (streptozotocin STZ, 65mg · kg-1) to establish a rat model of diabetes. The experiment was divided into three groups: control group, model group, treatment group, after a group of molded week given losartan 20 mg · kg-1 · d-1 ig. Control group and model group were measured at 4, 8 and 12 weeks of 24h urinary protein, urinary albumin / creatinine ratio (A / C), serum CRP and TNF-α levels; observed renal pathology morphological changes; using immunohistochemical assay the kidney tissue TOLL-like receptor 4 (TLR4), protein expression of nuclear factor-кB (NF-кB); kidney tissue of TLR4 nucleic acid expression by RT-PCR method; these indicators measured after 12 weeks of treatment group. Model group compared with the control group: the model group rats 24h urine protein, A / C, serum CRP and TNF-α were significantly higher; kidney tissue of TLR4, NF-кB expression was significantly increased. Correlation analysis prompted TLR4 expression and the expression of NF-кB 24h urine protein, A / C, serum CRP and TNF-α levels were positively correlated. Losartan treated rats compared with the model group rats 24h urine protein, A / C, blood CRP, TNF-α decreased renal tissue of TLR4, NF-кB expression have also weakened, before and after treatment differences (P lt; 0.05). Conclusion Losartan has a protective effect on diabetic nephropathy, part of the mechanism of action may be achieved by down-regulating NF-кB of TLR4 expression, lower blood CRP, TNF-α content, inhibiting the inflammatory response.
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