| Diabetes has almost been found in all races of the world. With the develop-ment of economy and the raising of the level of diabetic treatment, the diabetic patients'life span is increased, so diabetic chronic complications have become one of the most important factors which affect the prognosis of diabetes, espe-cially type 1. Diabetic nephropathy ( DN) is a major cause of death in type 1 di-abetic patients. Most of the type 1 diabetic patients with DN will die of cardio-vascular diseases in advance, the danger of whose is 20 - 40 times as much as those without. In American, diabetes is one of the most common reasons of ter-minal nephropathy. 33% patients of renal transplantation are diabetic patients. In Nanjing, there is an investigation to 642 diabetic patients, which found the morbidity of DN was 47. 7% . The basic pathologic change of DN is the multipli-cation of the glomerular capillary basement membranes and mesangial expan-sion. Now the etiopathogenesy and pathogenesy of DN is not clear, but there are several possible mechanism: ( 1) hemodynamic change of glomerulus: there are high perfusion, hyperfiltration, hyperosmolarity in glomerulus. (2) glycome-tabolism disorder; continuously high glucose concentration can activate polyols metabolic pathway, increase the activity of PKC and formate many glycosylation end products. (3) genetic susceptibility; It is not completely clear now. It is probably affected by multiple genes and multiple factors. (4) the effect of cyto-kines; They can lead to glomerular hemodynamic change, make mesangial cells hypertrophia and proliferation, and increase of extracellular matrix, transforming growth factor - β1 ( TGF - β1) is one of the most studied cytokines. The in-crease of TGF - β1 is the base of the accumulation of mesangial extracellular matrix. It is also one of major pathogenic factors which lead to the accumulation of glomerular mesangial matrix. It can stimulate the synthesis of mesangial extra-cellular stromatin, inhibit the activity of the matrix metalloproteinases ( MMPs ) which can degrade extracellular matrix, and increase the activity of the TIMPs. So it can promote the accumulation of extracellular matrix.Many enzymes can degrade macromolecule proteins of the extracellular ma-trix, the MMPs for example. Their active sites contain metal ion zinc and need calcium ion for stability. The MMPs are secreted as zymogens to the extracellu-lar matrix and act in normal physiological conditions. The expressions and regu-lations of the MMPs are tightly controlled. They are the sole enzymes to disinter-grate fibrous collagen to this day. The TIMPs is a kind of coding proteins of the multiple gene families and a kind of glycoproteins to inhibit the MMPs. They are natural specific inhibitors of the MMPs and bind with high affinity to the active site of the MMPs resulting in preventing the mutual action of the MMPs and their substrates. The aim of the experiment is to furnish the theoretical basis for the rational and effective therapy to DN in molecular level by studying the relation-ship among transforming growth factor - β1 ( TGF - β1) , matrix metalloprotein-ase (MMP) , tissue inhibitor of metalloproteinase (TIMP) , extracellular matrix ( ECM ) and diabetic nephropaphy ( DN ) and observing the inhibition of TG F -βs in a high glucose environment.MethodsBased on randomized block, 60 Wister rats were divided into 2 groups: group C( control, 10 rats) and group DM (diabetes ,50 rats). Diabetic model was instituted by STZ. The concrete method was : STZ was dissolved in 50mmol/L citric acid buffer solution to PH4. 5,2% fresh solution, then injected to the rats' abdominal cavities of the group DM at a dose of 60mg/kg. After 72h, the blood samples were obtained from tail vein. Any whose fasting blood -glucose concentration ≥ 16.7mmol/L was regarded as diabetic rat (43 rats in all). At the same time, group C was injected with physiological saline at thesame dose. 10 rats of group DM were separately killed after 2 weeks, 6 weeks...
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