Abstract:
Objective To investigate the effect of hyperuricemia on podocyte and its possible mechanisms.
Methods A total of 40 male SD rats were randomly divided into four groups, including control group (group A), mild hyperuricemia group (group B), hyperuricemia group (group C), and allopurinol group (group D). Twenty-four weeks later, all rats were sacrificed, and heart blood was taken for detecting creatinine and uric acid. The left kidneys were collected for pathological examination, as well as detection of the expression levels of angiotensin Ⅱ (AngⅡ), interleukin-6 (IL-6), superoxide dismutase (SOD), nephrin, podocin using immunohistochemical staining, Western blotting, and RT-PCR.
Results There were no obvious differences in Scr levels among the four group, while the levels of uric acid in groups A, B, C, and D were (65.04±5.26), (106.87±11.00), (147.23±25.75), and (89.78±11.67) μmol/L, and significant differences statistically were found between either two of the four groups. No obvious renal histopathological abnormalities were observed by H-E staining in all four groups. The number of nucleated cells in the glomerular mesangial area was slightly higher in group B and C. Different degrees of podocytopenia and pathological changes of podocytes were also observed in group B and C using electron microscope. Immunohistochemical staining showed that AngⅡ was mainly expressed in the glomerular mesangial area and a few in the renal tubular epithelial cells, and the differences of the AngⅡ expression were statistically significant between either two groups (P < 0.05). IL-6 was mainly expressed in renal tubular epithelial cells and a few in the glomerular mesangial area, and the differences of the IL-6 expression were statistically significant between either two groups (P < 0.05). SOD was expressed in glomerular and tubular cells, the differences of the SOD expressions were statistically significant between either two groups (P < 0.05). Western blotting and real-time PCR results showed that the levels of protein and mRNA of nephrin and podocin in the renal tissues were different between either two groups (P < 0.05). Correlation analysis showed that there were negative correlations between serum uric acid and the expression of nephrin, podocin, SOD in kidney tissue, and there were positive correlations between serum uric acid and the expression of AngⅡ and IL-6 in kidney tissue (P < 0.05).There were negative correlations between the expression levels of AngⅡ, IL-6, nephrin, and podocin in kidney tissue (P < 0.05). There were positive correlations between the expression levels of SOD, nephrin and podocin in kidney tissue (P < 0.05).
Conclusions Hyperuricemia can lead to podocytes injury, and the probable mechanisms include activation of the RAS system, oxidative stress, micro-inflammatory response. Allopurinol could reduce the podocyte injury through lowering uric acid or lowering the activation of the RAS system, oxidative stress, and micro-inflammatory response.