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Effect Of Angelica Polysaccharide On IRS-1/PI3Kp85/GLUT4 Signaling Pathway In Insulin R-esistance Of Diabetic Rats

Posted on:2019-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:Z H ZhangFull Text:PDF
GTID:2394330566473842Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective: This experiment was conducted for studying the effective component-s of Angelica sinensis extract Angelica polysaccharide,and the effects of Angelica polysaccharide on glucose and lipid metabolism disorder,fat factor,adipoc-ytokine,insulin level and sensitivity in diabetic rats were observed,aim to explore whether it play a role in the promoting rat insulin resistance through regulate the insulin expression pathway,to clarify the specific mechanism of Angelica polysaccharides in the regulation of diabetes and provide efficacy of ba-sic experiment support for drug development and clinic use.Methods: In the experiments,100 SD male rats were used for normal feeding.After 1week,10 rats were kept as normal group.The remaining 90 rats werefed on highfat and high-sugar diets,8 weeks later,they were exposed to strep-tozotocin(25 mg/kg)in the tail of the rats and 7 days later,the blood of rats' tail vein were randomly selected to detect blood glucose.If the value was?13.9 mmol/L,the type 2 diabetes was successfull model.The unsuccessful rats were injected again with streptozotocin(12.5 mg/kg)make it standard.In the successful model of rats,50 rats were randomly selected and divided into 5 groups(10/group): model group,angelica polysaccharide low dose group,angelica sinensis polysaccharide middle dose group,angelica polysaccharide high dose group and pioglitazone group.The blank group was given the same volume of normal saline and the model group received no intervention.The high,middle,and low dose groups of angelica polysaccharides were given respectively bygavage with 400 mg/kg,200 mg/kg,and 100 mg/kg,The pioglitazone group was given by gavage with western pioglitazone(10 mg/kg).All above drugs once a day for 4 W.During theintervention,the rats' haircolor,activity,water consumption,body weight and random blood glucose wereobserved.After the intervention,blood was collected from the right posterior femoral artery,and stored for testing.After blood collection,the rat was put to death,then took out the pancreas and skeletal muscle tissue and stored for testing.Blood lipids and blood glucose were examined by biochemistry method,using ELISA kit to test adipocyte factor,PCR and Western blot to test m RNA and protein expressions of IRS-1,PI3Kp85 and GLUT4 and pancreatic tissue was stained with HE.Based on the test results of diabetic rats in each group,the effects of Angelicapolysaccharides on each index were analyzed.Result:(1)Compared with the blank group,the model group began to lose weight in the second week,with statistical significance(P<0.05),compared withthe model group,all drug group gained weight from the third week,with statistical significance(P<0.05),compared with the pioglitazone group,Angelica polysaccharide no statistically significant(P>0.05).(2)Each drug intervention group was able to lower blood glucose-regulated insulinlevels and increase insulinsensitivity.Compared with the pioglitazone group,the high dose group of Angelica polysaccharide was significantly more effective than the other groups(P<0.05).(3)Angelica polysaccharide high-dose group and pioglitazone group can regulate lipid disorders,reduce serum total cholesterol,triglyceride,increase high-density lipoprotein,there was no statistically significant difference between twogroups(P>0.05),the effect of Angelica polysaccharide high dose group on lowering low-density lipoprotein was equal to pioglitazone group,with no statistical significance(P>0.05).(4)The high dose of angelica polysaccharide and pioglitazone can regulate the expression of adipocytokines.There was no difference in the effects of increasing serum adiponectin and decreasing leptin levels between two groups(P>0.05).In the terms of reducetion of resistin level,the pioglitazone group was superior to the high dose group of angelica polysaccharide,with significant statistically difference(P<0.01).(5)Angelica polysaccharides and pioglitazone can promote the expression of IRS-1,PI3Kp85 and GLUT4 m RNA in rats.The high dose group of Angelica polysaccharide and pioglitazone group has the best curative effect.There is no statictically difference between two groups(P>0.05).(6)Angelica polysaccharides and pioglitazone can promote the expression of IRS-1,PI3Kp85 and GLUT4 proteins in rat pancreatic tissue.The high dose group of Angelica polysaccharide and pioglitazone group h-ave the best curative effect,but the treatment effect of two groups is equivalent(P>0.05).(7)Angelica sinensis polysaccharide and pioglitazone all can repair pancreatic is lets in the pancreas and increase thenumber of islets.Conclusion: Angelica polysaccharides can reduce blood glucose in diabetic rats,regulate insulin levels and resistance,increase sensitivity,regulate blood lipids,reduce cholesterol,triglyceride,low-density lipoprotein levels,increase highdensity low-lipoprotein levels,regulate adipocytokines expression,increased serum a-diponectin expression,decreased leptin,resistin levels,can increase islet number,reduce islet structure destruction,repair and improve pancreatic tissue and islet function,its therapeutic effect may regulate signal pathway by IRS-1,PI3Kp85,GLUT4,which palys a role in theating.
Keywords/Search Tags:Angelica polysaccharide, Diabetes, Insulin resistance, Blood lipidsfatty, cytokines
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