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The Protective Effect Of Angiotensin-(1-7) On Beta Cells In Diabetic Rats And Its Effect On JNK/Caspase-3 Pathway

Posted on:2018-12-04Degree:MasterType:Thesis
Country:ChinaCandidate:N DanFull Text:PDF
GTID:2334330536973908Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Objective:1.To establish the diabetic rats model and use Ang-(1-7)for interference,to observe the changes of the morphology and function of islet tissue;2.To compare general indexes of each group and the changes of protein and gene of the c-Jun N-terminal Kinase(JNK),c-Jun N-terminal kinase phosphorylation(p-JNK)and Caspase-3 in islet tissue;3.To explore Ang-(1-7)could downregulate the JNK/Caspase-3 signaling pathway to protect the islet function and reduce islet cells apoptosis or not.Methods:A total of 34 healthy male Wistar rats were fed with common diet for 1 weeks.10 rats were selected randomly as normal control group(NC,n=10)given the the normal diet to the end of the experiment.The other 24 rats were provided with STZ 30mg/kg by intraperitoneal injection to establish a model of diabetic rats after 8 weeks of high-fat and high-calorie diet.20 diabetic rats were survival and randomly divided into two groups.There were 10 rats in diabetic control(DM)group and 10 rats in Ang-(1-7)intervention(D1)group.The rats in Ang-(1-7)group were intervened with Ang-(1-7)by the way of subcutaneous injection on the neck and the time of intervening lasted for 8 weeks,while the DM and NC group were given by same volume of normal saline in the same place.After the experiment,testing the levels of blood glucose,serum insulin and Ang II and measuring homeostasis model assessment of insulin resistance index(Homa-IR)of each group.Adopting HE staining to observe the shape of each rat's islet tissues.Approachingimmunohistochemical staining method to detect the protein expression levels of JNK,p-JNK and Caspase-3.Applying Real-time PCR to detect the mRNA expression levels of JNK and Caspase-3.Results:Compared with NC group,there was a significantly decresase in weight and serum insulin levels and an increase in blood glucose,Ang II levels,HOMA-IR values(P<0.05).The structure was damaged and the shape was abnormal.The protein expression of JNK,p-JNK,Caspase-3 in islet were obviously upregulated(P<0.05);The mRNA expression of JNK and Caspase-3 were clearly upregulated(P<0.05).D1 group compared to DM group,there was no obvious changes in the body weight of rats(P>0.05),while the levels of blood glucose,Ang II levels and HOMA-IR were decreased,the level of serum insulin was increased(P<0.05).The shape and function of islet tissue were improved but did not return to normal level.The protein expression of JNK,p-JNK,Caspase-3 in islet were downregulated(P<0.05);The mRNA expression of JNK and Caspase-3 were downregulated(P<0.05).Conclusions:The experimental results indicate that Ang-(1-7)may lower blood glucose,relieve insulin resistance and decrease islet cells apoptosis to improve the function of islet ? cell by downregulating the expression of JNK,p-JNK and Caspase-3.
Keywords/Search Tags:Ang-(1-7), Diabetes mellitus, JNK, Islet function
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