| Background:Type 2 diabetes is now recognized as the development of cardiovascular disease(CVD) is a major risk factor。Study found that each1% increase in Hb A1 C is associated with a 7.5% increase in CVD mortality, a 14% reduction in the incidence of myocardial infarction, and each 10 mm Hg reduction in systolic blood pressure.Compared with non-diabetic patients, patients with type 2 diabetes, the risk of cardiovascular disease increased by 2 to 4 times.Not only in the treatment of diabetes to control blood sugar, more important is to prevent high blood sugar the damage to the great vessels.At the heart of the therapy in the treatment of type 2 diabetes is solve the insulin resistance and beta cell dysfunction,biguanides and thiazolidinediones,also called “sensitizers”, by reducing hepatic glucose output and promoting uptake of glucoseby the periphery.Another kind is the promote the secretion of insulin dose, effect on pancreatic beta cells to promote the release of insulin.The use of these traditional oral glucose-lowering drugs, however, in most cases not significantly reduce the incidence of great vessels, therefore actively looking for a kind of both can lower blood sugar, and patients with coronary heart disease can bring the benefits of hypoglycemic drugs more and more important.GLP-1 agonists liraglutide is a new kind of oral glucose-lowering drugs,which had been approved for the treatment of diabetes by FFA that have an important role in cardiovascular aspects.Objective:Subcutaneous injection liraglutide for 7 days before ischemia, to observe the effect of liraglutide on the myocardial infarction size、myocardial cells apoptosis、the expression of Bcl-2 and Bax protein in rat.To discuss whether liraglutide protect myocardial ischemia-reperfusion injury by antiapoptotic mechanisms.Methods:1.48 Healthy male SD rats were randomly divided into shame-operated group 、ischemia reperfusion(I/R)group and Liraglutide group.Shame-operated group:under the left anterior descending coronary artery(LAD) threading, without ligation of blood vessels,anesthesia for 150 minutes;ischemia reperfusion(I/R)group and Liraglutide group:LAD was occluded for 30 min, reperfusion for 120 min,without intervention any.The Liraglutide group in rats of preoperative give 7days liraglutide(70μg/kg)subcutaneous injection,once a day. The shame-operated group and ischemia reperfusion(I/R)group according to the same volume of physiological saline subcutaneous injection for 7 days.2.The HE staining under light microscopy observe the change of the myocardial cells;the area at risk(AAR) was determined using Evans blue and infarct area(IR) using triphenyl tetrazolium chloride staining. Apoptosis o f myocardial cells was detected with TUNEL staining method, and expressions of myocardial apoptosis proteins Bcl-2 and Bax were detected with immunohist ochemical method.Results:1.Determine the myocardial infarction size:Compared with the sham-operated group,myocardial infarct size in myocardium of ischemia-reperfusion group IR/AAR(62.13±8.27),IR/LV(45.00±4.87) was significantly increased(P<0.05).Compared with ischemia-reperfusion group rats,myocardial infarct size in Liraglutide group IR/AAR(44.00±8.30),IR/LV(29.75±3.77) were significantly reduced,the difference has statistics significance(P<0.05).2.Myocardial cell changes in morphology light microscope observed the extent of myocardial injury of Liraglutide group compared with ischemia-reperfusion group significantly reduced.3.Detection of myocardial apoptosis:The sham-operated group has a few cardiomyocyte apoptosis,Compared with the sham-operation group(4.77±0.54),the number of cardiomyocyte apoptosis was significantly increased in ischemia-reperfusion group;but compared with ischemia- reperfusion group, Liraglutide group(26.10±0.74)significantly reduced the number of cardiomyocyte apoptosis(P<0.05),the difference has statistics significance(P<0.05).4.The expression of myocardial apoptosis protein Bcl-2 and Bax protein:compared with the sham-operated group,ischemia reperfusion(I/R)group the expression of Bcl-2(0.282±0.034) and Bax(0.288±0.032)protein significantly increased(P<0.05); comparedwith ischemia reperfusion(I/R)group, Liraglutide group the expression of Bcl-2(0.363±0.034)significantly increased, the expression of Bax(0.162±0.039)significantly reduced,the difference has statistics significance(P<0.05).Conclusions:Liraglutide can protects cardiomyocytes from ischemia reperfusion injury by reduce the myocardial infarction size,the mechanism of protection may be related to raise the Bcl-2 protein expression,down the expression of Bax protein, resistance to cell apoptosis. |
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