| BACKGROUND Soya foods, a staple in several Asian countries, have received increasing attention because of their nutritional properties and their high isoflavone content. Recent studies on animal model of kidney disease and human clinical trial showed that instead of animal protein the soybean diet could decrease serum cholesterol, ameliorate proteinuria and protect renal funtion. Soy isoflavones have been extensively studied because of their possible benefits to renal disease. Genistein (Gen) , the major isoflavone aglycone, has received most attention. Studys had proved that Gen had many physioactivity, such as binding with estrogen receptor and playing estrogenoid or antiestrogen role, inhibiting protein tyrosine kinases, ribosome S6 kinase, having strongely antioxidant effect and so on.Diabetic nephropathy (DN) is an important disease through out the globe, whose pathologic and physiological changes are involved in activation of active oxygen system, production of advanced glycation end-products(AGEs), activation of polyol pathway and so on. The oxidative stress state in DN accelerates generating many oxidation products, such as AGEs, oxidation-low density lipoprotein (OX-LDL) and advanced oxidation protein products(AOPPs). Studies showed that they might derectly or by bind to there own receptor cause oxidative stress state inside cells, activate nuclear transcription factor-B (NF-B) and protein kinase C(PKC), thus influence gene expression of kidney mesangial cells (MCs) , including expression ofsome important grow factors, by which the oxidation products might cause renal glomerulus lesions.ObjectiverThe purpose of our study was to investigate the effect of Gen as antioxidant on oxidative stress state in cultured rat MCs stimulate by oxidation products(AGEs, OX-LDL and AOPPs). We gived Gen in different concentration to SD rat MCs stimulated by oxidation products to observe changes in vitality of AOEs (SOD, GSH-PX, CAT) and the level of malondialdehyde (MDA) inside cells, nuclear translocation of NF- K B, expression of receptor of AGEs (RAGE) and the special receptor of OX-LDL, lectin-like oxidized low-density lipoprotein receptor (LOX-1) and expression of transforming growth factor(TGF) and platelet derived growth factor (PDGF), trying to prove MCs protective effect of Gen and explore the possible mechanism.Methods: The study was preceded in vitro. The MCs were divided into three groups as high glucose group (control group) , oxidant production groups and Gen groups. Each group was incubates for 12, 24, 48 hours. The vitality of AOEs (SOD, GSH-PX, CAT) and the level of MDA was evaluated by chromatometry. Immuno-histochemistry was performed to determine the expression of RAGE, LOX-1 and p65. The quantity of TGF- 3 i and PDGF were determined by ELISA. The expression of RAGEmRNA was assayed by semi-quantitive reverse transcription polymerase chain reaction (RT-PCR).Results:The result of chromatometry showed that the vitality of AOEs (SOD, GSH-PX, CAT) declined and the level of MDA increased in MCs of oxidation products group compared with the control groups significantly. While Gen groups in different concentration showed antioxidant effect, which can be concluded from the increasing in the vitality of AOEs and the decreasing in malondialdehyde. At the same time, Gen effected as antioxidation from 100mol/L. Gen 200mol/L had the strongest effect. At the same concentration, short time group (12h) had no abovious effect on MCs, as time went on, the effect get stronger, 48h group showed the strongest outcome. The results showed that the antioxidate effect of Gen on MCs was in dose -and time-dependent manner. The result of p65 by immunohistochemistry showed thatoxidation products could promote p65 translocation into nuclear in contrast with control group. At the same time, the inhibition of high concentration Gen (100,200 mol/L) were strong, the low were (10,50 mol/L) weak. At the same concentration, the inhibition of short term Gen (12h) were weak, the long were (24h,48h) strong. Immunohistochemistr...
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