| Objection:To study the effect of Angiopoietin2on the progression of diabetic nephropathy, and investigate the dffect of Alprostadil Injection on the expression of Angiopoietin2and IL-18in streptozotocin (STZ)-induced diabetic mice.Methods:8weeks old male C57BL/6J mice were randomly divided into three groups: normal control group, diabetic nephropathy model group and alprostadil treated group. Mice of model and treated group were induced by streptozotocin140mg/kg peritoneal injection. After diabetic nephropathy model was induced successfully, mice of treated group received daily intraperitoneal injection of alprostadil at the dosage of80ug/kg body weight, and mice of model group and control group received normal saline. Five mice of each group were sacrificed at the end of2weeks,4weeks,8weeks. Blood glucose, serum creatinine (Scr), blood urea nitrogen (BUN), urinary creatinine, triglyceride (TG) and total cholesterol (TC) were measured to evaluate physiological condition.24hour proteinuria level, creatinine clearance (Ccr) and indicator of renal hypertrophy were calculated to evaluate renal function. Pathologic changes of the kidneys were observed by periodic acid-schiff staining. The mRNA expressions of Ang-1, Ang-2, tie-2, VEGF, IL-18in the kidney were examined by RT-PCR. The located expressions of Ang-2and IL-18were detected by immunohistochemistry staining.Results:Blood glucose,24h urinary protein, Ccr and KW/BW were significantly increased in diabetic nephropathy model group compared with those in control group, with no significant difference in Scr, TC, TG between the two groups.24h urinary protein, Ccr were ameliorated in treated group compared with model group, while blood glucose, Scr, TC, TG and KW/BW had no significant difference between model group and treated group. Glomerular hypertrophy and mesangial expansion were observed in model group. As compared to control group, mRNA expressions of Ang-2and IL-18were significantly up-regulated in model group, while the express of Ang-1, tie-2, VEGF had no significant difference between the two groups. The mRNA expressions of Ang-2and IL-18were significantly down-regulated in treated group. There was significantly positive correlation between Ang-2mRNA and IL-18mRNA. Immunohistochemistry analysis revealed Ang-2was expressed in the glomerulus, mainly in endothelial cells and IL-18was expressed both in the glomerulus and promixal tubular. As compared to control group, the protein expressions of Ang-2and IL-18were significantly increased, while the protein expressions of Ang-2and IL-18were reduced in treated group at4weeks and8weeks.Conclusion:Ang-2and IL-18may be involved in the development and progression of diabetic nephropathy in mice. Alprostadil Injection can protect renal function by reducing proteinuria, inhibiting glomerular hypertrophy and hyperfiltration in diabetic nephropathy. This effect, at least partially, was mediated through down-regulating expressions of Ang-2and IL-18. |
PDF Full Text Request