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Studies On The Mechanism Of Chemical Composition Of Rheum Palmatum L.in Anti-diabetic Nephropathy

Posted on:2004-02-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z H TanFull Text:PDF
GTID:1104360095451451Subject:Pharmacology
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Diabetic nephropathy is a common but serious complication of diabetic mellitus, and it's a main cause of death of diabetic. It is difficult to treatment of diabetic nephropathy because it's pathogenesis is not clear, and the incidence of this disease is increasing year by year. It is critical to study on the treatment of diabetic nephropathy.To determine the anti-diabetic nephropathy chemical composition of Rheum palmatum L., the diabetic nephropathy mice induced by alloxan were used. The results showed that the anthraquinone of Rheum palmatum L.is effective.To examine the effects of anthraquinone of Rheum palmatum L. on anti-diabetic nephropathy, the SD male rats were induced diabetic nephropathy by IP streptozotocin (STZ). The results showed that anthraquinone can decrease the levels of urinary micro-albumin,serum creatinine and food intake, reduce the volume of the urine and water intake in STZ rats, and reduce the index of kidney, the area of mesangium and it's IOD ,the rate of mesangium area and glomerular area,and the anthraquinone also can protect the renal tubule epithelial cell from necrosis in STZ rats.To study the anti- diabetic nephropathy mechanisms of Emodin,Rhein and Chrysophanoljthe cultured human mesangial cells (HMC) were used.To mimic the hyperglycemic environment of diabetic nephropathy.the 30 mmol/L glucose were added to the 10% FBS RPMI 1640.The results showed that Emodin and Rhein can inhibit the proliferation of HMCs (by MTT),while Chrysophanol has no action on the proliferation of HMCs; Rhein and Chrysophanol can reduce the bioactivity and total activity of transforming growth factor-betal( TGF 1),Emodin has no actionon the bioactivity and total activity of TGF 1 Emodin can regulate the synthesis of fibronectin (FN) (by using immunohistochemistry), but Rhein can not. Emodin and Rhein both inhibit the secretion of FN in HMCs.Emodin can decrease the activity of MMP-2, but has no action on the MMP-9,proMMP-2 and proMMP-9(by using gelatinase zymography).Emodin and Rhein both can inhibit the increased activity of p38 MAPK(by using immunoprecipitate and Western blot).Here we showed, also for the first time, that Emodin , Chrysophanol and ] Rhein can against of DN through inhibit the bioactivity and total activity of TGF P land activity of p38 MAPK to inhibit the priliferation of HMCs, increase the activity of the MMP-2 and regulate the secretion and synthesis of FN.
Keywords/Search Tags:Rheum palmatum L., Emodin, Rhein, p38Mitogen-activated protein kinases (p38MAPK), Transforming growth factor-beta (TGF β1), Matrix Metalloproteinases (MMPs), Diabetic nephropathy(DN).
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