ABSTRACT
Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats.Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ,35 mg/kg) in spontaneous hypertensive rats (SHR).Diabetic rats were divided into diabetic group and the Irbesartan treated group.The pathological changes were investigated by fluorescence microscope and electron microscope.The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose.The concentration of angiotensin Ⅱ in the supernatant was detected by radioimmunoassay.Immunofluorescence staining was performed to detect the co-localization of CD31 and FSP1.Results The significant myocardial fibrosis was presented in the diabetic group.Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats.Double staining of HAEC showed co-localization of CD31 and FSP1,which was decreased by the treatment of Irbesartan (P ＜ 0.05).When HAEC was exposed to high glucose,it showed some cells acquired spindle-shaped morphology and lost CD31 staining,and FSP1 and α-SMA protein expression levels were markedly upregulated,which attenuated by the treatment of Irbesartan.Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats.
ABSTRACT
Objective To investigate the effects of low density lipoprotein receptor (LDLr) pathway on podocyte injury in diabetic nephropathy (DN) under inflammatory stress.Methods Male db/db mice and db/m mice were randomly divided into four groups (8 mice in each group):db/m group (control),casein injected db/m group (db/m + casein),db/db group (db/db),and casein injected db/db group (db/db + casein).An inflamed model of DN was established according to our previous study.24-hour urinary protein was measured every week.The plasma lipid profile was detected by clinical biochemistry assay.Podocyte changes were evaluated by electron microscope and immunofluorescent staining.Lipid accumulation in the kidney was evaluated by oil red O staining and intracellular cholesterol quantitative assay.The protein expression of Wilm's tumor-1 (WT-1),nephrin,α-smooth muscle actin (t-SMA),and molecules correlated with LDLr pathway were examined by immunohistochemical staining or Western blotting.The colocalized protein expression of LDLr with WT-1 was examined by immunofluorescent staining and laser confocal microscopy.Results There were no differences in plasma levels of LDL and HDL among four groups.Compared with db/db group,the db/db+ casein group showed markedly increased 24-hour urinary protein,more significant podocyte foot process effacement and podocyte damage,increased lipid droplet accumulation in kidneys,increased protein expressions of LDLr,SCAP and SREBP-2 in kidneys (all P ＜ 0.05).Interestingly,increased LDLr protein expression in kidneys of db/db mice was negatively correlated with decreased nephrin protein expression (r =-0.855,P ＜ 0.01) and positively correlated with increased α-SMA protein expression (r=0.768,P ＜ 0.01).Conclusions The disruption of LDLr pathway induced by inflammation contributes to podocyte injuries in diabetic nephropathy.