[Effect of pioglitazone on the expression of TLR4 in renal tissue of diabetic rats].

OBJECTIVE:To investigate the effect of pioglitazone on the expression of Toll-like receptor 4 (TLR4) in renal tissue of diabetic rats. METHODS:The male Sprague Dawlry rats (n=57) were randomly divided into the control group (n=9) and experimental group (n=48). The experimental rats were injected introperatoneally with 50 mg/kg streptozotocin (STZ) and the controls were given sodium citrate buffer instead. Then the experimental rats were randomized into five groups: pioglitazone 5 mg/(kg.d), pioglitazone 10 mg/(kg.d), pioglitazone 5 mg/(kg.d) plus TLR4-specific antagonist Eritoran 5 mg/(kg.d), pioglitazone 10 mg/(kg.d) plus TLR4-specific antagonist Eritoran 5 mg/(kg.d), non-intervented group, with 5 rats in each group. The pioglitazone was administrated intragastrically, and normal saline was given to the contro group in the same way. Five weeks after pioglitazone administration, Eritoran was injected intraperitoneally for consecutive one week. At the end of the eighth week, 24-hour microalbuminuria and the serum concentrations of C-reactive protein (CRP) were determined by radioimmunoassay. Expressions of TLR4 and peroxisome proliferator-activated receptor γ (PPARγ) in kidney were determined by Western blotting and immunohistochemistry. RESULTS:Compared with the control group, the 24-hour urine protein, plasma concentration of CRP, the expression of TLR4 in kidney increased significantly in the experimental groups (P<0.05). Furthermore, these indicators in all intervention groups obviously decreased compared with the non-intervention group (P<0.05). In addition, the expression of TLR4 in high-dose pioglitazone significantly decreased compared with low-dose pioglitazone (P<0.05). The study also found that high-dose pioglitazone and TLR4 antagonist Eritoran could reduce the expression of TLR4 in the diabetic rats, but the difference from the group of low-dose pioglitazone plus Eritoran was not significant statistically (P>0.05). CONCLUSION:Pioglitazone may exert the anti-inflammatory action by decreasing the expression of TLR4 in renal tissue and regulating the balance between proinflammatory and anti-inflammatory.