Protective Effect Of Rosiglitazone On Adriamycin Nephrosis Rat Kidney

Objective: To investigate the mechanism of renal protective effect of rosiglitazone on rats with adriamycin-induced nephropathy . Methods: Twenty wistar rats were randomly assigned to following groups:control (CTR ) group,adriamycin nephrosis(ADR ) group and rosiglitazone (5mg·kg-1·d-1) treatment (GRL) group.①Measured the levels of urinary protein once another week.at the end of 12th week,examined the levels of serum total protein,albumin,total cholesterol and triglyceride in rats,Observed the pathological change of kidney and the renal function change in rats.② Immunohistochemistry were used to examine the nuclear - translocation of NF- κ Bp65 and the protein expression of TGFβ1 in the kidney of rats.③ The activity of renal cortical NF-κBp65 was measured by sandwich ELISA.④ The levels of PPARγ mRNA and TGFβ1 mRNA in the rats of kidney tissue were detected by RT-PCR. Results: ① At the end of experiment, 24 hour urinary protein excretion of RGL treatment group decreased significantly as compared to ADR group(224.684±27.22mg vs 261.354±25.45mg , p<0.01).In comparison with ADR group ,the serum albumin levels were increased(25.975±1.77g/L vs 21.025±4.45g/L, p<0.05),but the serum total cholesterol and triglyceride were decreased in the rats of RGL group(3.424± 1.202 mmol/L, 5.288 ± 0.7827mmol/L vs 5.125 ± 0.615mmol/L, 6.625±0.83mmol/L, p<0.01). ② In the rats of ADR group,focal segment glomerulosclerosis, mesangial matrix expansion and the adhesion of capsule and glumerulus in some glomeruli,and a lot of protein casts in renal tubule were observed by lightmicroscopy, but in the rats of RGL group, mesangium expansion and the adhesion of capsule and glumerulus were ameliorated, segment glomerulosclerosis were not observed. ③ In comparison with ADR group, the expression of PPARγmRNA in renal tissue was up-regulated significantly(p<0.01), but the activity of renal cortical NF-κB p65 and the expression of TGFβ1 protein and mRNA were decreased in the rats of RGL group(p<0.01). The correlation analysis were manifested: in rats of ADR and RGL group,there was a positive correlation between the activity NF-κB p65 or the expression of TGFβ1 mRNA and the ratio of area of mesangium to the area of glomerulus(r=0.8412, 0.8757, p<0.01). At the same time, there was a negative correlation between the activity NF-κB p65 and the expression of PPARγmRNA in renal tissue(r=-0.8305, p<0.01). but there was a positive correlation between the activity NF-κB p65 and the expression of TGFβ1mRNA in renal tissue(r=0.6290, p<0.01). In rats of ADR and RGL group,there was a negative correlation between the expression of TGFβ1mRNA and PPARγmRNA in renal tissue(r=-0.7938, p<0.01). Conclusion: ①Rosiglitazone may play a role of protective effect in rats with adriamycin nephrosis. ②In the rats of RGL group, the expression of PPARγmRNA in renal tissue was up-regulated significantly,but the activity of renal cortical NF-κB p65 and the expression of TGFβ1 proteinand mRNA were decreased, These data suggest rosiglitazone could inhibit the activity of renal cortical NF-κB p65 in part through up-regulating the expression of PPARγmRNA in the kidney tissue,so inhibit the expression of TGFβ1mRNA in the kidney tissue, reduce the proteinuria and mesangial matrix accumulation.