Protective effect of pioglitazone on kidney injury in diabetic rats.

Objectives: To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.

Methods: Forty healthy Sprague Dawley rats were selected and randomly divided into five groups, with 8 rats in each group. Group A served as control group and were administered with sterile citrate buffer (i.p.) as placebo. Groups B, C, D and E rats were injected (i.p.) with streptozotocin to induce type I diabetes. Diabetic rats in Group B were intragastrically administered with sterile saline solution alone. Groups C, D and E rats were intragastrically given pioglitazone hydrochloride suspension at doses of 10, 20, 30 mg/kg per day, respectively. After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobin A1c, serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index (KHI), observation of renal pathological changes using light microscope and electron microscope. Mean glomerular cross-sectional areas (MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin (PCX) protein expression.

Results: Results showed that levels of hemoglobin A1c, BUN, SCr in Groups B, C, D and E rats were significantly higher than those in Group A (P<0.05), while BUN and SCr levels in rats of Groups C, D and E were significantly lower than those in Group B (P<0.05). KHI, MGA and MGV levels were significantly higher in Groups B, C, D and E rats than those in Group A (P<0.05); KHI and MGA levels in Group B rats were significantly higher than those in Groups C, D and E (P<0.05) and MGV in Groups D and E was significantly lower than that in Groups B and C (P<0.05). Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary in Group A rats. Renal mesangial matrix proliferation and expansion of glomerulus cavities in Groups B, C, D and E were observed. However, damage degree in Groups C, D and E were more moderate than that in Group B.

Conclusions: Pioglitazone can reduce kidney damage in diabetic rats, which may be attributed to its role in increasing glomerular PCX protein expression and inhibiting urinary excretion of PCX, and its effect is dose dependent.