| OBJECTIVE Diabetes and its complications affect people's health and life quality severely. Many studies have shown that there is close relationship between adhesion molecules (AMs) and diabetic complications. Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal failure. Cilostazol, a potent phosphordiesterase (PDE) type Ⅲ inhibitor, has been attributed with vasodilatation and anti-platelet activity in peripheral arterial disease. Recent studies have shown that cilostazol also affects the expression of adhesion molecules. Rat diabetic models were traperitoneal injection of streptozotocin (STZ). The pathological changes and the expression of ICAM-1 and VCAM-1 in kidney were observed, and then the relationship between expression of AMs and pathological changes of kidney were analyzed to explore the mechanism of the protective effect of cilostazol on diabetic kidney.METHODS Diabetic model was prepared by streptozotocin (STZ) intrapertoneally to fasted male SD rats at the dose of 55mg.kg-1, normal control animals received citrate buffer (N, n=10). Diabetes was diagnosed based on blood glucose concentration when STZ-treated rats were at 72 hours. Diabetic rats were divided randomly into four groups: diabetic control group (DM, n=20), high-dose of cilostazol (HC, n=15), low-dose of cilostazol (LC, n=15) and insulin group (PZI, n=8). After 12 weeks, all animals were sacrificed. The following parameters were measured: body weight, fasting blood glucose concentrations (BG), HbA1c, the ratio of kidney weight to body weight, ICAM-1 and VCAM-1 protein expression were detected by western blot and localized by immunofluorescence, the mRNA level of these two adhesionmolecules were semi-quantitated by RT-PCR.RESULTS (1) The levels of BG in DM group was higher than those in N group (p<0.01). The levels of BG in HC and LC group were not decreased significantly. There was no difference in the levels of BG between N and PZI group; (2) The levels of HbAlc in DM group was higher than those in N group (p<0.05). Compared with the DM group, only insulin had significant effect on the HbAlc; (3) There was significant increase in the ratio of kidney weight to body weight in DM group compared with N group(DM 1.2 + 0.10; N 0.73+0.05, ;?<0.01), cilostazol decreased kidney hypertrophy (HC: 1.1+0.05; LC: 1.13 + 0.20; p>0.05 vs DM group); (4) immunofluorescence study under fluorescence microscopy demonstrated that DM rats' glomerulus expressed ICAM-1 strongly, high and low-dose of cilostazol made down ICAM-1 expression in different degree;(5) The results by RT-PCR showed that cilostazol could decrease the expression of ICAM-1 (DM:0.7790±0.068, HC: 0.5000 + 0.1550, LC: 0.5798 + 0.0590; p<0.05 vs DM) and VCAM-1 (DM:0.6862 + 0.0405;HC:0.423± 0.0956;LC:0.4249 + 0.0422; p<0.05 vs DM); (6)Results of western blot showed that expression of ICAM-1 and VCAM-1 in N group were weak, while increased significantly in DM group, and had a tendency to decrease after treatment with cilostazol.CONCLUSIONS In STZ- induced SD diabetic rats, we demonstrated that expression of ICAM-1 and VCAM-1 increased in the kidney. There was positive correlation between the expression of AMs and kidney lesion. Cilostazol showed its protective effects on kidney by decreasing the expression of AMs and could decrease or delay the development of diabetic nephropathy.
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