Effects Of Mycophenolate Mofetil On The Expression Of Insulin-like Growth Factor-1and Matrix Metalloproteinase-2in Kidneys Of Diabetic Nephropathy Rats

Background and ObjectiveWith the changing of lifestyle and eating habits in many developing countries, the incidence of diabetes increases day by day. Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM). Diabetic nephropathy is becoming the most important cause of chronic kidney disease. Hyperfiltration and hyperperfusion have been viewed as pivotal in the development of diabetic nephropathy and are found very early in the diaease process. The earliest morphological change of diabetic nephropathy is expansion of the mesangial area. This is caused by an increase in extracellular matrix deposition and mesangial cell hypertrophy. The pathogenesis of diabetic nephropathy is multifactorial. Both genetic and environmental factors are responsible for triggering series of pathophysiological events. Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today.The study aimed to investigate the effects of mycophenolate mofetil (MMF) on the expression of insulin-like growth factor-1(IGF-1) and matrix metalloproteinase-2(MMP-2) in kidney of diabetic rats. Materials and methods1Male SD rats were divided into three groups:normal control rats (control group), diabetic rats (DM group), and diabetic rats received MMF (MMF group,15mg·kg-1·d-1). DM rat models induced by intraperitoneal injection with streptozotocin were constructed. Eight weeks later,24-hour proteinuria quantitation, blood glucose, creatine clearance rate (Ccr), and the ratio of kidney weight/body weight were measured.2Kidney pathology was observed by HE staining and PAS staining of sectiones of nephridial tissue. Immunohistocytochemistry and Western blot were used to analyze the expression of insulin-like growth factor-1(IGF-1) and matrix metalloproteinase-2(MMP-2).3Statistical analyses:All statistical analysis was performed using SPSS statistical version17.0. Data were expressed as means±SD. Statistical significance of changes between the different groups was carried out by one-way analysis of variance, further analysis by Bonferroni test. Correlation analysis performed by Pearson test. Statistical significant level was defined as α=0.05.Result1Compared with the control group,24-hour proteinuria quantitation, blood glucose, creatine clearance rate (Ccr), and the ratio of kidney weight/body weight of DM group increased markedly (P<0.01).24-hour proteinuria quantitation, Ccr, and the ratio of kidney weight/body weight of MMF goup were lower as compared to DM group.2The pathology in kidney of diabetic rats showed the degree of glomerular basement membrane thickening, mesangium cell hyperplasia, and extracellular matrix hyperplasia of the DM group increased compared with the MMF group significantly. Immunohistochemistry noted that compared with control group the expression of IGF-1in renal tissue of DM group and MMF group was increased (P<0.01). The expression of IGF-1inrenal tissue of MMF group reduced compared with the DM group (P<0.01). The expression of MMP-2was on the contrary (P<0.01).3Western blot analysis noted that compared with control group the expression of IGF-1in renal tissue of DM group was increased. MMF treatment could reduce the increased expression of IGF-1. The expression of MMP-2was on the contrary.4Correlation analysis revealed that24-hour proteinuria quantitation had a positive relationship with the expression of IGF-1{r=0.743, P<0.01), had a negatively correlation with the expression of MMP-2(r=-0.756, P<0.01). The expression of IGF-1had a negatively correlation with the expression of MMP-2(r=-0.58, P<0.01). Conclusion1The expression of IGF-1was increased in kidney of DM rat models induced by intraperitoneal injection with streptozotocin. The expression of MMP-2was on the contrary. IGF-1and MMP-2produced marked effect in the development and progression of diabetic kidney jinjury.2The protective role of MMF in diabetic kidney disease which reduced extracellular matrix deposition in renal tissue possibly partly associated with downregulated expression of IGF-1and upregulaed expression of MMP-2.