Protective Mechanism of Eplerenone on Rats with Diabetic Nephropathy

OBJECTIVE To study the protective mechanism of eplerenone on rats with diabetic nephropathy (DN). METHODS DN model rats were randomly assigned as follows:model group, eplerenone group (40 mg·kg^-1) and positive control group (valsartan, 20 mg·kg^-1). And a normal group was set. The drugs were given to rats daily for 8 weeks by instragastric administration. The 24 h urinary protein, serum creatinine and the blood glucose hemoglobin levels were measured by automatic biochemical analyzer. Then observed the levels of IL-6, TNF-α and MCP-1 changs in renal tissue by ELISA. The mRNA expression of TLR4, NF-κB p65 in renal tissue were examined by qPCR, the protein expression of TLR4, NF-κB p65 in renal tissue were examined by Western blot. RESULTS Compared with the model group, the levels of 24 h urinary protein, serum creatinine and glycosylated hemoglobin in eplerenone group were significantly decreased (P<0.05 or P<0.01);the pathological changes of renal tissue were improved in different degree;the levels of IL-6, TNF-α and MCP-1 in renal tissue of rats in eplerenone group were decreased significantly (P<0.05 or P<0.01);the mRNA level of TLR4, NF-κB p65 and the protein level of TLR4, NF-κB p65 in renal tissue of rats with eplerenone was also decreased significantly (P<0.01). CONCLUSION Eplerenone can effectively improve the inflammation level of rats with DN, which may be related with decreasing IL-6, TNF-α, MCP-1, TLR4, NF-κB p65 levels.