| Hyperlipidemia are associated with happening and progression of renal diseases. Low density lipoprotein(LDL) and oxidized low density lipoprotein(Ox-LDL) binding with their respective receptors and lysophosphatidylcholine(LPC), one production of oxidation of LDL, can lead to many pathological changes in glomeruli such as monocyte transmigration, proliferation of glomerular cells and deposition of extracellular matrix(ECM) mediated by cytokines, growth factors, chemotactic factors and adhesion molecules. Glomerular mesangial cells(MsC) are response cells to stimuli and restore cells to injury in glomeruli. It is involved in cells proliferation in early periods of renal diseases and fibrosis, sclerosis in chronic renal diseases. In the studies on mechanism and therapy of glomerular pathological changes, mesangial cells would be inspected as one of key factors.Expression of transforming growth factor-β1(TGF-β1) would be determined as one of efficacious indices to evaluate the effect in remedial studies on many renal diseases. TGF-β1 regulates the synthesis and degradation of extracellular matrix, modulates cell growth and differentiation. It also participated in inflammation, immunity reactions and tumor occurrence. TGF-β1 would upregulate in glumerular pathological changes and manifest mighty function in fibrosis, to facilitate synthesis of extracellular matrix and inhibit degradation, which leads to the deposition of ECM and chronic progress of renal diseases. Presently studies on the lower events of TGF-β1 have been reported frequently. TGF-β1 binds to its receptor Ⅰand Ⅱcomplexes that will lead to phosphorylation and activation of receptor Ⅰby receptor Ⅱ. Activated receptor Ⅰwill induce activation of transcription factors activator protein-1(AP-1) and Smads which will regulated expression of the target genes. It has been reported singularly about the upper cascades of TGF-β1 and the exact mechanism of upregulation of TGF-β1 remain to elucidated.Nuclear factor-κB(NF-κB) exists universally and mediated the transcriptions of many cytokines, adhesion molecules, receptors of cytokines, receptors of chemotactic factors and apoptosis counteractive proteins etc, such as inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein-1(MCP-1), vascular cell adhesion molecule-1(VCAM-1) etc. So it exerts vital function in inflammation and immunity reaction. NF-κB/Rel is a family of transcription factors and consist of p105/p50, p65/RelA, p100/p52, c-Rel and RelB etc in mammalians. NF-κB exists in homologous or heterogenous dimers, binds to special DNA sequences on the target genes and regulates transcription. The special sequence is entitled κB site. Its core sequence is GGGRNNYYCC(R is a purine, Y is a pyrimidine, N is any base). NF-κB activity is regulated by IκB in cytoplasm. IκB is also a giant family consisted of IκBα, IκBβ, IκBγ, IκBεand bcl-3 in mammalians. There are 6-7 ankyrin repeats in IκB molecule which can bind to Rel homology domain and cover the nuclear localization sequence of NF-κB stagnated in cytoplasm. NF-κB could be activated by inflammation, immunity reaction, oxidative stress, and many cytokines such as tumor necrosis factor-alpha(TNF-α), interleukin-1 etc. At present, whether Ox-LDL can induce activation of NF-κB and mechanism involved has not been reported.Ox-LDL could upregulated the TGF-β1 in mesangial which has been confirmed by our previous studies. Wherever, the mechanism remains to be elucidated. On the basis of function characters of Ox-LDL, TGF-β1, NF-κB and glomerular mesangial cells in renal injuries, the present study aimed at the changes of NF-κB binding activity and TGF-β1 transcription induced by Ox-LDL in rat glomerular mesangial cells and relativity of the changes which would illustrate the mechanism of renal injuries by lipid partially.Chapter one Changes of NF-κB binding activity induced by Ox-LDL in glomerular mesangial cells Objective: To determine the changes of NF-κB binding activity, monomer proteins...
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