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Effect Of Curcumin On Experimental Proliferative Glomerulonephritis And Prevention Role And Its Mechanism

Posted on:2004-10-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Y BaoFull Text:PDF
GTID:1114360092995556Subject:Academy of Pediatrics
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In the glomerulonephritis, it has been known that immune pathogenesis is involved in it and is very complicated and diversity. Generally, it is only an initiator, and a serious of inflammatory introduction system activated on the bases of immune is the immediate reason causing renal damage and clinical manifestation. Inflammatory cells infiltrating in renal and renal intrinsic cells directly or indirectly cause renal deterioration through producing and secreting multitudinous cytokines and inflammatory medium. If there is a material that can block the process of above or prevent inflammatory cells infiltration, it should be beneficial to renal disease.Nowadays, though there are many ways in treating glomerulonephritis, there remains that available therapeutics do not effect on some patients. Hence, it was becoming one of hot spots to develop and excavate new drug coming from natural plant to treat proliferous glomerulonephritis.With the development of cell and molecular biology at full speed, it was found that the biological effects of various inflammatory media exert their activities by draw assistance from its definite receptor and intracellular signal pathway and corresponding cascade response. And numerous cellular signal transductions activate or block the activation of nuclear transcription factors. Recently years, two nuclear transcription factors, nuclear factor kappa-B (NF-kB) and activaor protein-1 (AP-1) are attracting more attention, which are involved in many biology processes including cell growth, differentiation and immunity response and so on, specially regulating genes correlating to immune inflammatory response, such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-a), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-β) and extracellular matrix (ECM) etc. Parts of newly produced cytokines conversely activate NF-KB and AP-1, unceasing vicious circle, which formsamplify effect and leads to inflammatory reaction augmentation.The roles of NF-kB and AP-1 in the renal disease are being paid more and more attention in recent years. They can control mesangial cell proliferation and its secretion of cytokines and/or chemokines. The activity of NF-KB and AP-1 in glomerulus or renal cortex of various human and experimental glomerulonephritis models is enhanced. Since they play a central role in proinflammatory gene expression, there is growing interest in modulating their activity. It may be useful for preventing and treating renal diseases to hinder NF-KB and AP-1 activation.Curcumin, a yellow polyphenol pigment isolated from turmeric, has anti-inflammatory, anticoagulant, antioxidant and anti-fibrosis etc. activity. It inhibits human blood vessel smooth muscle cells, endothelial cells, hepatocytes and T lymphocytes proliferation and these may take place by curbing the activation of NF-KB and AP-1. Curcumin also reduces PMN infiltrating in inflammatory tissue and restrains the formation of leukotriene in polymorphonuclear neutrophils (PMN). Besides, it can ameliorate body metabolism status by lowering the levels of serum cholesteral, triglycerol lipid and phospholipid, and elevating fibrinolysis, attenuating lipid peroxidation and exerting anti-platelet aggregation. It increases body corticoid production and induces body sensibility to adrenal cortical hormone. On the basis of above theories, we postulate that curcumin may be useful in preventing and treating proliferation glomerulonephritis. Therefore, on the one hand, we investigate whether curcumin utilizes in experimental nephrotoxic nephritis; on the other hand, we observe the effect of curcumin on the mesangial cell growth and matrix protein turnout and cytokines expression. These results will provide clues for curcumin to be developed to prevent and treat proliferating glomerulonephritis.Part one: Investigation the effect of curcumin on nephrotoxic sera nephritis in ratsObjective To observe the effect of curcumin on the urine pro...
Keywords/Search Tags:Curcumin, nephrotoxic sera nephritis, proteinuria, ultrastructure, proliferation cell neutral antigen, extracellular matrix, fibronectin, lipopolysaccharide, mesangial cell, cell proliferation, transforming growth factor-β1
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