The Experimental Study On The Injury And Pathogenesis Of Glomerular Podocyte And Slit Diaphragm And It's Drug Intervention In Diabetic Rats

PART ONE THE EXPERIMENTAL STUDY ON INJURYAND PATHOGENESIS OF GLOMERULAR PODOCYTE AND SLIT DIAPHRAGM IN DIABETIC RATS Objective To investigate the changes of glomerular podocyte and slitdiaphragm and research it's pathogenesis and effect in diabetes. Methods The animal model was induced by streptozotocin(STZ).The levels of urinary albumin excretion rate (UAER) were assayed. The activities of superoxide dismutase (SOD), catalase (CAT) andconcentrations of malondialdehyde (MDA) in renal cortex were measured.Immunohistochemistry was used to detect the proteinic expression ofdesmin, a marker of podocyte injury, and slit diaphragm protein nephrin.The levels of nephrin mRNA were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the ultrastructure ofglomerular podocytes was observed by transmission electronic microscopy. Results Compared with normal control rats, the activities of SOD andCAT decreased and the concentrations of MDA increased significantly indiabetic renal cortex (P<0.05, respectivly). The proteinic expression ofdesmin increased markedly while the expression of nephrin protein andmRNA decreased significantly in diabetic group (P<0.05, respectivly). Footprocess effacement in podocytes was observed in diabetic group. At thesame time, UAER increased in diabetic group (P<0.05). Conclusion The decreased antioxidantion and increased oxidativestress in kidney may injury podocyte and slit diaphragm to impair theintegrality of outer layer barrier of glomerular filtration and increase UAERin diabetic rats. It may be the pathogenesis of renal injury and proteinuriain diabetes. PART TWO THE EFFECT AND MECHANISM OF LOSARTAN ON GLOMERULAR PODOCYTE AND SLIT DIAPHRAGM IN DIABETIC RATS Objective To investigate the effect and mechanism of losartan, theangiotensin II type 1 receptor antagonist,on glomerular podocyte and slitdiaphragm in diabetic rats. Methods Diabetic rats were induced by STZ. Wistar rats wererandomly divided into following groups: group N (normal control rats),group D (diabetic rats), group DL (diabetic rats treated with losartan) .UAER was assayed. The activities of SOD and CAT and concentrations ofMDA in renal cortex were measured. The proteinic expression ofglomerular desmin and nephrin were dected by immunohistochemistry.RT-PCR assessed the levels of nephrin mRNA. At the same time, weinvestigated the ultrastructure changes of glomerular podocytes bytransmission electronic microscopy. Results Compared with group N, the activities of SOD and CATdecreased significantly and the concentrations of MDA increased markedly in diabetic renal cortex (P<0.05, respectivly). The proteinic expression ofdesmin increased and the expression of nephrin mRNA and proteindecreased significantly accompanied with foot process effacement inpodocytes and UAER increased in group D (P<0.05, respectivly). Allabove changes were relieved in group DL compared with group D (P<0.05,respectivly). Conclusion Losartan may maintain the structural and functionalintegrity of podocyte and slit diaphragm, outer layer barrier of glomerularfiltration, and decrease proteinuria by antagonizing the effect of Ang II,augmenting the effect of renal antioxidation and inhibiting the oxidativestress in diabetic rats. It may be the mechanism of losartan protects kidneyand prevents the development of diabetic nephropathy. PART THREE THE EFFECT AND MECHANISM OF ASCORBIC ACID ON GLOMERULAR PODOCYTE AND SLIT DIAPHRAGM IN DIABETIC RATS Objective To investigate the effect and mechanism...