| ObjectiveTo observe the effect of glucagon-like peptide-1(GLP-1) receptor agonistexenatide on the expression of cardiac adiponectin, adiponectin receptor1（AdipoR1）,glucose transporter type4（GLuT4） and monocyte chemotactic protein1(MCP-1) intype1diabetic rats and to explore the protective roles and mechanisms of exenatideon cardiomyopathy of type1diabetic rats．MethodsForty-two male Sprague-Dawley（SD） rats were randomly divided into normalcontrol group（group A，n=7）and diabetic model group（n=35）. Type1diabetic modelwas established by intraperitoneal injection of streptozotocin. Twenty-nine diabeticrats induced successfully were randomly divided into diabetic （group B，n=10）,diabetic treated with low doses of exenatide（group C, n=10）and diabetic treated withhigh doses of exenatide (group D， n=9. Rats in group C were injectedsubcutaneously with exenatide in dose of1μg kg-1twice daily. Rats in group D wereinjected subcutaneously with exenatide in dose of5μg kg-1twice daily. Rats in groupA and B were injected subcutaneously with equivalent volume of normal saline. Allrats were sacrificed after cardiac function was detected at8weeks when exenatidetreatment was finished. The mRNA expressions of myocardial AdipoR1, Glut4andMCP-1 were detected by real-time fluorescence quantitative PCR. The proteinexpression of myocardial AdipoR1, phosphorylated-AMPK-α and AMPK-α wereanalyzed by Western blotting. The distribution and expression of AdipoR1in cardiactissue was detected by immunohistochemical staining. Plasma and myocardialadiponectin levels were assayed by Enzyme-linked immunosorbet assay （ELISA）.Results1. General characteristics. Compared with group A, group B had significant increased fasting blood glucose,cholesterol, triglyceride and free fatty acid, The plasma insulin were significantlydecreased in group B（P＜0.05）. After exenatide treatment, compared with group B,fasting blood glucose, cholesterol, triglyceride, free fatty acid plasma insulin showedno significant change in group C（P＞0.05）. Cholesterol, triglyceride and free fattyacid had significantly decreased in group D（P＜0.05）, but fasting blood glucose andplasma insulin showed no significant change（P＞0.05）.2. The ratio of heart weight to body weight and heart function.Compared with group A, body weight, whole heart weight, left ventricularsystolic pressure（LVSP）, The maximum descent-speed of pressure in the left ventricleisovolumic relaxation period（-dp/dtmax）（mmHg/s） and the maximumascendent-speed of pressure in the left ventricle isovolumic contraction period（+dp/dtmax）（mmHg/s） were significantly decreased in group B（P＜0.05）, the ratio ofheart weigh to body weight and Left ventricular diastolic pressure（LVEDP） weresignificantly increased in group B（P＜0.05）. Compared with group B, LVSP and±dp/dtmax were significantly increased, and LVEDP was were significantlydecreased in group C（P＜0.05）, but body weight, whole heart weight and the ratio ofheart weigh to body weight showed no significant change. Compared with group C,LVSP was significantly increased, and LVEDP was were significantly decreased（P＜0.05）, but±dp/dtmax had no significant change in group D（P＞0.05）.3. The levels of plasma adiponectin, cardiac adiponectin and expression ofmyocardial AdipoR1The levels of plasma adiponectin were significantly decreased in group Bcompared to group A, the mRNA and protein expression of myocardial AdipoR1weresignificantly increased in group B compared to group A（P＜0.05）. After exenatidetreatment, compared with group B, the levels of plasma adiponectin weresignificantly increased and the mRNA and protein expression of myocardial AdipoR1were significantly decreased in group C and group D（P＜0.05）. Compared with groupC, the levels of plasma adiponectin and the mRNA and protein expression ofmyocardial AdipoR1had no significant change in group D. There was no differencein the cardiac adiponectin level compared among four groups（P＞0.05）. 4. The expression of myocardial GLuT4, phosphorylated-AMPK-α and MCP-1The mRNA expression of myocardial GLuT4, and the protein expression ofmyocardial phosphorylated-AMPK-α were significantly decreased in group Bcompared to group A（P＜0.05）. The mRNA expression of myocardial MCP-1 weresignificantly increased in group B compared to group A（P＜0.05）. After exenatidetreatment, the mRNA expression of myocardial GLuT4, and the protein expression ofmyocardial phosphorylated-AMPK-α were significantly increased in group C andgroup D compared to group B（P＜0.05）. The mRNA expression of myocardialMCP-1 were significantly decreased in group C and group D compared to group B（P＜0.05）. Compared with group C, the mRNA expression of myocardial GLuT4,myocardial MCP-1 and the protein expression of myocardialphosphorylated-AMPK-α had no significant change in group D.5．The morphologic observations of rats’myocardium by HE stainMyocardial fiber arranged orderly, cellular nucleus was in cell centers andspherical or ellipse in group A. The myocardial fiber arranged disorder, part of fiberfracture，focal necrosis, part of myocardial cells showed degeneration necrosis, thesize of cellular nucleus was irregular, myocardial interstitial inflammatory infiltrationin group B. After exenatide treatment, all these changes were attenuated in diabeticrats.Conclusions1. The model of type1diabetic rats was successfully induced, it would be availableto study T1DM and diabetic cardiomyopathy.2. The heart function was significantly decreased, the ratio of heart to body weightwas obviously increased, the levels of cardiac adiponectin had no significant change,the levels of plasma adiponectin, the mRNA expression of myocardial GLuT4, andthe protein expression of myocardial phosphorylated-AMPK-α were significantlydecreased, the mRNA and protein expression of myocardial AdipoR1, the mRNAexpression of myocardial MCP-1 were significantly increased. After exenatidetreatment, the heart function was significantly improved, the ratio of heart to bodyweight and the levels of cardiac adiponectin had no significant change. The levels of plasma adiponectin, the mRNA expression of myocardial GLuT4, and the proteinexpression of myocardial phosphorylated-AMPK-α were significantly increased, themRNA and protein expression of myocardial AdipoR1, the mRNA expression ofmyocardial MCP-1 were significantly decreased.3. Exenatide up-regulates the levels of plasma adiponectin, the expression ofmyocardial phosphorylated-AMPK-α and GLuT4, down-regulates expression ofmyocardial AdipoR1and MCP-1, promotes myocardial glucose oxidation, decreasingthe cardiac inflammation reaction, improve heart function, thus produces heartprotection in diabetic rats. |
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