| Objective:To observe the effects of rosiglitazone on the expression of myocardial adiponectin(APN) and its receptor 1 in Type 2 diabetic rats,which was induced by feeding with high-fat and high-sugar diet and then injection of a low dose of streptozotocin(STZ) by abdominal cavity.Methods:Thirty-six male Wistar rats were randomly divided into control(group A,n=10), diabetic(group B,n=13) and diabetic treated with rosiglitazone(group C,n=13).All animals had free access to water.Group A was fed with common chow.Group B and C were fed with high-fat and high-sugar diet consisting of 10%pork fat,20%cane-sugar,2%cholesterol,1%sodium cholate,and 67%common chow.After 4 weeks,group B and C ware injected with a low dose of streptozotocin(STZ) by abdominal cavity(STZ,30 mg/kg BW,Sigma company,to dissolve in 0.1 mol/LCitric Acid buffer,pH 4.4),group A was injected with equivalent volume of Citric Acid buffer by abdominal cavity.After 1 week,fasting blood glucose(FBG) and fasting insulin (FINS) were measured and then insulin sensitivity index(1/FBG×FINS) was calculated.The rats with fasting blood glucose(FBG)≥7.8mmol/l and insulin resistance were considered as type 2 diabetic models.Group B had 11 diabetic rats and group C had 12 diabetic rats.After type 2 diabetic models were established,group B and C ware continuously fed with high-fat and high-sugar diet and group A was continuously fed with common chow.Group C was administrated with rosiglitazone(3mg/kg/d) by lavage for 12 weeks.Group A and B were administrated with equivalent volume of normal sodium by lavage for 12 weeks.After 12 weeks, 1 day before the experiment finished,all animals were fasted for 12～14 h and then were anesthetized by injection with 10%chloral hydrate(0.3mL/100gBW) by abdominal cavity.The maximum descent-speed of pressure in isovolumic relaxation period in the left ventricle (-dp/dtmax) and the maximum ascendent-speed of pressure in isovolumic contraction period in the left ventricle(+dp/dtmax) were measured by carotid artery cannula.The rats were sacrificed after blood was obtained by abdominal cardinal vein.The blood preparation was used to measure plasma glucose,insulin triglyceride and cholesterol.The heart was immediately taken out of thoracic cavity after the rat was sacrificed.The heart was rinsed with normal sodium and dried by filter-paper and then weighed.The ratio of heart to body weight was calculated.The apex of heart was fixed by formalin and then was dehydrated,imbedded by paraffin and sliced for HE stain.The rest part of cardiae ventricle was immediately thrown into the liquid nitrogen and then stored in the -70℃refrigerator in use for detecting the protein expression of adiponectin,the mRNA expression of adoponectin receptor 1,and the protein expression of GLUT4,AMPK and P-AMPK in the heart of rats.Results 1.Compared with group A,fasting blood glucose,insulin,triglyceride and cholesterol levels was significantly increased in group B.After rosiglitazone treatment,fasting blood glucose,insulin,triglyceride and cholesterol levels was significantly decreased in group C.2.The results of the myocardium stained by HE and observed through the light microscope in diabetic rats were as following:The myocardial cells lined up in order,the size of cellular nucleus was the same,and the kytoplasm was stained in uniformity in group A.The myocardial cells lined up in disorder,the size of cellular nucleus was irregular,and the cardiac muscle fiber was broken and lined up in disorder in group B.The above pathological changes were obviously improved in group C than those in group B.The myocardial cells comparatively lined up in order,the size of cellular nucleus was comparatively regular and the obviously broken cardiac muscle fiber was unseen in group C.3.The expression of myocardial adiponectin(APN) and its receptor 1.The plasma and myocardial adiponectin levels,and the mRNA and protein expression of cardiac adiponenctin receptorl were significantly decreased in groupB than those in group A(P<0.05).After rosiglitazone treatment,the plasma and myocardial adiponectin levels and the mRNA and protein expression of cardiac adiponenctin receptorl were significantly increased in groupC than those in group B(P<0.05).4.The protein expression of GLUT4 and AMPK in myocardium.The myocardial phosphorylation level of AMPK-αand the protein expression of cardiac GLUT4 were significantly decreased in group B than those in group A(P<0.05).After rosiglitazone treatment, the myocardial phosphorylation level of AMPK-αand the protein expression of cardiac GLUT4 were significantly increased in groupC than those in group B(P<0.05).5.Heart function.Compared with group A the maximum descent-speed of pressure in the left ventricle isovolumic relaxation period(-dp/dtmax)(mmHg/s) was significantly decreased in group B(P<0.05).However,there was no difference in the maximum ascendent-speed of pressure in the left ventricle isovolumic contraction period(+dp/dtmax)(mmHg/s) between group A and group B(P>0.05).After rosiglitazone treatment,the(-dp/dtmax) was obviously higher in groupC than group B(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.The pathological changes in myocardial cell were consistent with diabetic cardiomyopathy.2.The heart function and the concentration of blood and myocardial adiponectin are decreased in type2 diabetic rats.Blood glucose and lipid,myocardial triglyceride,and the ratio of heart weight to body weight are increased in diabetic rats.The expressions of myocardial adiponectin and its receptor1,GLUT4,AMPK and P-AMPK are decreased in diabetic rats.3.After rosiglitazone treatment,the heart function is improved,the concentration of blood and myocardial adiponectin is increased,blood glucose and lipid,myocardial triglyceride and the ratio of heart weight to body weight are decreased,the expressions of myocardial adiponectin and its receptor1,GLUT4,AMPK,P-AMPK are increased in diabetic rats treated with rosiglitazone. |
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