| The accumulation of glomerular extracellular matrix(ECM) and the decrease in glomerular cell number were prominent and important pathologic features of progressive glomerulosclerosis which resulted from a variety of glomerular injuries.Some studies indicated that glomerular mesangial cells and other resident cells occurred apoptosis and glomerular mesangial cells were replaced by the extracellular matrix during glomerular inflammation.The excessive apoptosis of glomerular cells which leaded to the deletion of glomerular cells was an important cause of glomerulosclerosis .An important feature of glomerulosclerosis caused by lipid abnormality was glomerular cell number decrease .Lipids deposited in kidney could induce glomerular cell apoptosis. The apoptosis of glomerular mesangial cells might be an main cause of glomerular cell number decrease during late glomerulosclerosis.LDL deposited abnormally in glomeruli might excite mesangial cells and macrophages to release oxygen-derived free radidicals which made body at oxidative stress and leaded to lipid peroxidation. LDL was oxidized to be Ox-LDL. Ox-LDL which might result in cell necrosis or apoptosis played an important role in the development of glomerulosclerosis.Ox-LDL had higher affinity to mesangial cells and macrophages than LDL and was more readily taked up by mesangial cells and macrophages. Both Ox-LDL itself and MCP-1 produced by macrophages which are stimulated by Ox-LDL werechemoattractants for macrophages. Mesangial cells and macrophages preferentially taked up Ox-LDL over LDL through scavenger receptors .The uptake of Ox-LDL by mesangial cells and macrophages might further stimulate other immune effector cells to produce PGE2 ,cytokines and other mediators capable of stimulating matrix synthesis and to intensify the alteration of hemodynamics and blood vessel permeability in glomeruli . Mesangial cells and macrophages might die finally after taking up Ox-LDL and forming foam cells. All this could lead to glomerulosclerosis .Ox-LDL could inhibit mesangial cell proliferation and accelerate mesangial cell apoptosis at low concentration (<100μg/ml),which might be involved in the process of glomrular hypercellularity to hypocellularity during glomerulosclerosis.The regulation mechanism of mesangial cell apoptosis induced by Ox-LDL was unclear. Bcl-2 was a proto-oncogene related with apoptosis. One of its mechanisms was anti-oxidation injury. Bax which could counteract the anti-apoptosis role of Bcl-2 was a member of Bcl-2 family .The ratio of Bax to Bcl-2 protein decided the ratio of hetero- dimers(Bax / Bcl-2) and homodimers (Bax/ Bax) and the fate of cells. We guessed that Bcl-2 (antiapoptotic antigen)and Bax(proapoptotic antigen) might be involved in the regulation of mesangial cell apoptosis induced by Ox-LDL. In order to elucidate the regulation mechanism of mesangial cell apoptosis induced by Ox-LDL , we investigated the effect of Ox-LDL on the expression of Bcl-2 and Bax protein in vitro cultured glomerular mesangial cells by immunohistochemistry and the apoptosis by TUNEL and gel electrophoresis.We also studied the relationship of the blood LDL level with the apoptosis and the expression of Bcl-2 and Bax in the glomeruli of chronic glomerular nephritis patients accompanied with different degree glomerularsclerosis.The main results are as follows:1. Through stimulating human mesangial cells by Ox-LDL , Ox-LDL could inhibit the proliferation of human mesangial cells and induce theapoptosis of human mesangial cells in dose-dependent fashion at concentrations of 0 to 100μg/ml.MTT results indicated the larger the dose of Ox-LDL, the higher the level of inhibited mesangial cells at low concentration scope after stimulated forty-eight hours. TUNELand DNA electrophoresis results indicated the larger the dose of Ox-LDL, the higher the level of mesangial cells apoptosis at low concentration scope after stimulated forty-eight hours. 2. Ox-LDL could upregulate the ratio of Bax to Bcl-2 protein expression...
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