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Effect Of Rosiglitazone On The Expression Of Adiponectin Receptor 1 In Aortas Of Type 2 Diabetic Rats

Posted on:2010-11-01Degree:MasterType:Thesis
Country:ChinaCandidate:H Q ZhaoFull Text:PDF
GTID:2144360275961716Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:To investigate the effect of rosiglitazone on the expression of adiponectin receptor 1,NF-κB,and MCP-1 in aorta of type 2 diabetic rats.To explore the effect of rosiglitazone on the inflammatory response and its protective mechanism in aortic of type 2 diabetic rats.Methods:Thirty-six male Wistar rats were randomly divided into control(group A,n=10), and diabetic.Group A was fed with common forage and had free access to water.Diabetic was fed with high-fat and high-sugar diet(10%pork fat,20%cane-sugar,2%cholesterin,1%sodium cholate,67%common forage),and drank freely.After 4 weeks,diabetic was injected a low dose of streptozotocin(STZ,30mg/kgBW,to dissolve in 0.1 mol/L Citric Acid buffer,pH 4.4) by abdominal cavity and group A was injected isovolumic Citric Acid buffer by abdominal cavity.At the Sixth week,fasting blood glucose(FBG) and fasting blood insulin(FINS) were measured and then insulin sensitivity index(1/FBG×FINS) was calculated.The rats with fasting blood glucose(FBG)≥7.8mmol/1 and insulin resistance were considered as type 2 diabetic models.Diabetic model was randomly divided into diabetic(group B,n=11) and diabetic treated with rosiglitazone(group C,n=12).Group B and C ware continuously fed with high-fat and high-sugar diet.Group A was fed with common forage.At the same time, rosiglitazone(3mg/kg/d)was administrated by lavage for 12 weeks in group C.Isovolumic isotonic Na chloride was administrated by lavage for 12 weeks in group A and B.After 12 weeks,1 day before the experiment was finished,all animals were anesthetized by injection with 10%chloral hydrate(0.3mL/100gBW) by abdominal cavity after fasting for 12-14h.The rats were sacrificed after blood was obtained by abdominal aorta.The blood preparation was used to measure plasma glucose,insulin and lipids.The abdominal aorta was immediately taken out of abdominal cavity after the rat was sacrificed and was washed clearly with isotonic Na chloride and dried with filter paper.Part of the aorta was fixed by formalin and then was dehydrated,imbedded by paraffin and sliced for HE stain and immunohistochemistry stain.The rest part was stored in the - 70℃refrigerator in order to detect the mRNA expression of adiponectin receptorl in aorta.Results:(1) Compared with group A,the levels of FBG,FINS,triglyceride(TG),total Cholesterol(TC) and ISI were significantly increased in group B(P<0.05).Compared with group B,the levels of FBG,FINS,TG,TC and ISI were significantly decreased in group C(P<0.05). (2) Compared with group A,the mRNA expression of AdipoR1 in aorta was significantly decreased in group B(P<0.05),and the protein expression of NF-κB and MCP-1 in aorta was significantly increased in group B(P<0.05).Compared with group B,the mRNA expression of AdipoR1 in aorta was significantly increased in group C(P<0.05),and the protein expression of NF-κB,MCP-1 was significantly reduced in group C(P<0.05).Conclusion:1.The model of type2 diabetic rats was successfully induced by feeding with high-fat and high-sugar diet and then injection of a low dose of streptozotocin(STZ) by abdominal cavity.This model was characterized by hyperglycemia,hyperlipemia and insulin resistance,which was very similar to the biochemistry and clinical features in type 2 diabetic human.It is a very good model to be used to study type 2 diabetes mellitus and its blood vessel complications.2.The expression of AdipoR1 mRNA in aorta was significantly reduced,and the expression of NF-κB,MCP-1 was significantly increased in type 2 diabetic group(P<0.05),suggesting that AdipoR1 was closely related to the occurrence and progression of diabetic macroangiopathy.3.After rosiglitazone treatment,the expression ofAdipoR1 mRNA was significantly increased, the expression of NF-κB,MCP-1 was significantly reduced,and pathological damage was lessened in the aorta of type 2 diabetic rats.The above results suggested that rosiglitazone could play the protective roles in great vessel by up-regulating the expressionof AdipoR1,and lessening inflammatory factor infiltration in diabetic aortic tissue.
Keywords/Search Tags:type 2 diabetes mellitus, macroangiopathy, adiponectin receptor1, rosiglitazone
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