The Effect Of Hydrochloride Benazepril On Podocalyxin Expression In Podocyte Of Diabetic Rats

Objective To observe the effects of hydrochloride benazepril on the urinarypodocyte-specific marker proteins Podocalyxin（PCX） evacuation and PCX proteinexpression in podocyte of diabetic rats at early stages,and investigate its protectiveefffects on the kidneys of diabetic rats as well as other possible related mechanisms.Methods Healthy Sprague-Dawley （SD）male rats were divided into the normalcontrol (Group NC) and the model group. Streptozotoin (STZ)-induced Diabetic modelrats were then treated with (Group DM) or without hydrochloride benazepril (GroupDT). Blood glucose was measured weekly in all groups. At the end of the4th week,urinary albumin (UALB)；urinary retinol binding protein (URBP)；urinary creatinine(UCR)； urinary podocyte-specific marker proteins PCX (UPCX)； triglyceride (TG)；total cholesterol (TC)； glycated hemoglobin (HBA1C%) and kidney index (KI) weremeasured. The renal tissues of diabetic rats were obtained after the rats sacrifice toobserve pathology change of the tissue section, and measure PCX protein and mRNAexpression by Immunohistochemistry and RT-PCR.Results1.4weeks later, Compared with group NC,the levels of BG、TC、HbA1C and TG ingroup DM and group DT were significantly higher (P<0.01or0.05), there were nostatistical differences between group DM and group DT (all P>0.05).2.4weeks later, the levels of UALB、URBP、UPCX and KI in group DM and groupDT were significantly higher than that in group NC (P<0.01). Compared withgroup DM, the above indexes were significantly reduced (P<0.01) in group DT.The results of correlation analysis showed that the positive correlations in UPCRwith FBG, HbA1c%, UACR, URCR and KI respectively（r=0.793，0.702，0.796，0.905，0.941，P<0.01）.3.4weeks later, the color of kidneys were deeper and the volume of kidneys were larger as well as the cortex were thicker in group DM than that in group NC bygross appearance. Under the high power lens，the glomerular volume werehypertrophied and ectracelluar matric increased and mesangial matrix proliferatedas well as the typically K-W nodules were seen within some glomerulus in groupDM by HE staining.All these changes were improved in group DT.4.4weeks later, Compared with group NC, Mean glomerular cross-sectional area(MGA) and mean glomerular volume (MGV) were significantly higher in groupDM and group DT (P＜0.01). DT group compared with DM group,the aboveindexes were significantly reduced (P＜0.01).5.4weeks later, in group NC,the results showed the glomerular basement membrane(GBM) uniform, and the fusion of epithelial foot processes (FP) structure wasnormal by electron microscopes. GBM was much thicker and FP were markedlydestroyed, even vanished in group DM compared with group NC, the differencewas statistically significant (P<0.01). in group DT, GBM without obviousthickening, a small amount of podocyte foot process fusion.Compared with the DMgroup, the difference was statistically significant (P>0.05).6.4weeks later, PCX mainly expressed in podocyte of glomerular, PCX expressedlinear strong positive along the capillary loops in group NC.PCX expression wassignificantly reduced or absent in group DM and was increased in DT. The PCXprotein expression in group DT was significantly higher than that in group NC(P<0.01).7. The expression of PCX mRNA in renal cortex in group DT, which much lower thanthat in group NC (P<0.01), was significantly higher than that in group DM(P<0.01).Conclusion Hydrochloride benazepril can reduce the excretion of PCX by urine, andstimulate the PCX protein and mRNA expression of kidney, as well as relieve thedisease of kidney.