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Protective Effect And Mechanisms Of Polygona-polysaccharose On Experimental Diabetic Animal Models

Posted on:2010-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:H L GongFull Text:PDF
GTID:2144360278950031Subject:Pharmacology
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ObjectiveTo study the protective effect and mechanisms of Polygona-polysaccharose(PSP)on experimental diabetic animal models.Methods1. The experiment of the maximally tolerated dose (MTD) was used to observe the acute toxicity of PSP in mice.2. The mice model of diabetes were established by injecting Alloxan (ALX) (220 mg/kg) into its abdominal cavity. Diabetic mice were randomly divided into model group, DMBG(250mg/kg) and PSP(250,500,1000 mg/kg).After 14d administration of PSP, FBG, organ weight, MDA, T-SOD and GSH-Px levels were determined. Pancreatic pathology was studied by morphological method.3. The rats model of diabetes were established by injecting Streptozotocin (STZ) (60 mg/kg) into its abdominal cavity. Diabetic rats were randomly divided into model group, DMBG(233mg/kg) and PSP(195,390,780mg/kg).The amount of water drinking, food intake, urinary volume and body weight were measured at the fourth week after the treatment. The blood samples were drawn to determine the indexes of FBG, GSP, INS, TG, TC and LDL. 4. Pancreatic pathology was studied by morphological method and immunohistochemical method. The distribution of apoptotic cells and the expression of Caspase-3 were observed by Terminal -deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and immunohistochemistry. Using the method of nitrate reductase to detect the index of NO. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect iNOS mRNA expression.Results1 Acute toxicity testingThe MTD of PSP in mice is 31.25 g/kg, which prompted that PSP almost had non-toxic side effects of treatment dose.2 Protective effects of PSP on diabetic mice induced by ALX2.1 PSP could decrease the blood glucose level and increase thymus index, spleen index and liver index in diabetic mice induced by ALX.2.2 PSP could decrease the content of MDA and enhance the T-SOD, GSH-Px in blood serum and liver tissue of diabetic mice induced by ALX.2.3 The results of HE showed that, the pancrea in the model group almost could not find complete islet, the islet structural disorderd and the edge was not clear. The islet in PSP groups were relativly regularly. The result of HE showed that the PSP had some protective effect of pancreatic islet. 3 Protective effect of PSP on diabetic rats induced by STZ3.1 Levels of FBG, GSP and the amount of water drinking, food intake, urinary volume in the PSP treated groups were obviously lower than those in the model group while INS increased.3.2 Compared with model group, PSP decreased the rate of apoptotic cells, the levels of Caspase-3 and NO in blood serum. While the iNOSmRNA expression up-regulated in the diabetes model group, the iNOSmRNA expression in PSP treated groups down-regulated.Conclusions1 PSP may have protective effect on diabetic mice induced by ALX and the mechanism might be related to its antioxidant activity.2 PSP can effectivly decrease blood glucose and have some protection of diabetic rats. The mechanism may be related with inhibiting islet cell apoptosis, lowering Caspase-3 and suppressing iNOSmRNA.
Keywords/Search Tags:Diabetesmellitus, Polygona-polysaccharose, apoptosis, nitricoxide synthase, Caspase-3, iNOSmRNA
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