Font Size: a A A

The Study Of The Expression Of MCP-1 In The Lupus Nephritis And The Effect Of Mycophenolate Mofetil

Posted on:2004-06-18Degree:MasterType:Thesis
Country:ChinaCandidate:G XiaoFull Text:PDF
GTID:2144360092499827Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Patients with lupus nephritis often have tubularinterstitial injuries and it is an important factor to influence the renal function.The increased infiltration of mononuclear cells is a common phenotype of renal pathology in the most of glomerulonephritis and tubularinterstitial lesions.The activated mononuclear cells can cause the destruction of renal formation ,hasten the glomerulosclerosis and tubularfibrosis by release cytokines,inflammatory medium and oxygen-derived free radicals.It is still unclear about the mechanisms of the infiltration of mononuclear cells in the renal tissues.But the overexpression of chemotactic factors and adhesion moleculars in the renal tissues is considered as the two important factors to cause the infiltration of inflammatory cells in the kidney.Monocyte chemoattractic protein-1(MCP-1) is a special factor for the mononuclear cells.The overexpressing of MCP-1in the renal tissues is a main reason to lead to the infiltration of monocytes in the previous experiments in vitro or in vivo. Mycopheonlate mofetil(MMF) is a new kind of immunosuppressent with special pharmacology.MMF have succeeded in treatment of anti-rejection reaction on clinical for organ transplantation.Literatures have reported that MMF could prevent the progression of lupus nephritis in BXSB mices.Van Bruggen group have found that MMF could reduce the excretion of urine protein and IgG or C3 deposition in glomerulus in MRL/lpr mices.Furthermore MMF could ameliorate survival rate and the levels of anti-DNAIgG in serum. MMF could relieve the damage in renal by interfering with the accumulation and proliferation of inflammatory cells.its mechanism is not clear.The expression of MCP-1 in the lupus nephritis and the influence of MMF to the expression of MCP-1 in the lupus nephritis and its correlative mechanisms have not reported in China.Protein kinase C(PKC)is a kind of serine/threonine protein kinase family and spreading very widely ,including organs,tissues and cells.PKC activated can take part in the renal injuries.It can influence the hemodynamics andpermeability of glomerular capillary, acceleration glomerular capillary basement membrane thickening , extracellular matrix accumulating,cellproliferation and leucocyte adhesiveness to cause diabetic nephropathy development.Ihm group have studied that the overexpression of MCP-1 in mesangial cells stimulated by high concentration of sugar in diabetic nephropathy was mediated by PKC pathway.It is also blocked by calphostin C(PKC inhibitor) to relieve the lesion of the kidney.Some studies have showed that nuclear factor kappa B (NF-κB) overexpression after PKC activated. NF-κB is an important member in the transcription factor family.It can adjust many genes expression.It takes part in the synthesis of inflammation cytokine, chemokine, fibrosis factor, cellular proliferation,ECM intercross, apoptosis and fibroblast differentiation .Scientists in China have found that NF-κB activation and MCP-1 expression were associated with the number of mononuclear cells in glomerulus and the degree of proteinuria in nephrotoxic sera nephritis rats.But it is still unclear about that the expression of PKC,NF-κB have any kinds of relation with the expression of MCP-1 in the LN glomerulus and MMF can relieve the expression of MCP-1 in renal tissues by inhibitionthe activation of NF-κB and PKC? Objective: ①MMF stimulated the normal mesangial cells cocultivation with the peripheral blood mononuclear cells conditioned medium(PBMC-CM) of eighteen lupus nephritis patients to express MCP-1 and to evaluate the efficacy and explore the underlying molecular mechanisms of MMF in the treatment of lupus nephritis.②To study the protective effect of MMF on MRL/lpr mices and it's influence to the expression of MCP-1 in the renal tissues and explore the underlying molecular mechanisms.Methods: ①After MMF stimulated the normal mesangial cells cocultivation with the PBMC-CM of lupus nephritis patients ,MCP-1,NF-ΚBp65 and PKC were examined by immuno...
Keywords/Search Tags:monocyte chemoattractic protein-1, lupus nephritis, mycophenolate mofetil, protein kinase C, nuclear factor-kappa B
PDF Full Text Request
Related items