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Dynamic Expression Of Myocardial β1-adrenoceptor And M2-muscarinic Acetylcholine Receptor In Stunning Myocardium Of Rat Hearts

Posted on:2009-09-25Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2144360242487081Subject:Surgery
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Background:Myocardial stunning(MS),or postischemic myocardial dysfunction,is defined as the mechanical dysfunction that persists a few hours,days or weeks after reperfusion despite the absence of irreversible damage and despite restoration of normal or near-normal coronary flow,without cell necrosis.MS is a common phenomenon in clinic and one of reasons which increase incidence rate and case fatality rate of left heart insufficiency.Considerable animal experiment and clinical research indicated that MS has frequent constituted the pathophysiological foundation of heart dysfunction after clinical open heart surgery and heart transplantation,it has become the question which consist in clincial treatment of cardiovascular surgery in recent years.The levels of catecholamine,angiotonin,antidiuretic hormone are rose in procedure of extracorporeal circulation and improve angiotasis.Decreased responsiveness of myofilaments to calcium.Massive positive inotropic only accelerate the exhaust of adenosine triphosphate but disadvantage to store it,result in irreversible myocardial damage.A number of hypotheses were proposed,most of which have been subsequently abandoned.At present,the two viable hypotheses regarding the pathogenesis of myocardial stunning are the "calcium" hypothesis and the "oxyradical" hypothesis,but its really pathogenesy has not final conclusion.In many internal and abroad empirical studies found that there were a number of kinds of acceptor system in the myocardium tissues,such as:β-adenoreceptor,M- acetylcholinergic receptor,angiotensin receptor, adenosine receptor etc.These receptors are all participate in to modulate cardiomotility via signal transducting system in myocardial cell envelope and play in an important role in normal heart function.Nevertheless,there is a few study and research of receptor systems in cardium about the number and founction,varied way in the pathophysiological process in MS,mechanism of mutual modulation.With the development of deep research of molecular biology and pharmacology,it provide a platform for research the role in where receptors play in the pathogenesy of coronary atherosclerotic heart disease.Objectives:To observe the variation of receptor in the levels of cell and gene,respectively,physiologic function of receptor in myocardial cell envelope, dynamic express of receptor in MS.Through the study,we can provide a new way for illuminate the pathogenesy of MS,meanwhile,provide model for exploratory study which to indicate the modulation of receptor,the mechanism of signal transduction,the change of heart function after MS and etc.Methods:PartⅠ:To establish the SD rat myocardial stunning model.Forty eight male Sprague-Dawley rats were randomly divided into six groups:control group,groups of 1 hour,4 hours,8 hours,24 hours and 72 hours reperfuseion after a single 15 minutes of left anterior descending coronary artery occlusion,the control group has no occlusion.SD rats were anesthetized with pen thiobarbital sodium.The left ventricular wall was exposed via a thoracotomy,and the main trunk of the left anterior descending coronary artery was dissected free from adjacent tissues.The artery was loosely encircled with a slide wire at a position distal to the first diagonal branch.MS was generated by blocking left anterior descending coronary artery.The rats were monitored by electrocardiogram in the whole prosess of operation and store it.PartⅡ:The detection ofβ1-adrenoceptor and M2-muscarinic acetylcholine receptor.To apply immunohistochemical method and reverse transcription-polymerase chain reaction analysis myocardium tissue of stuning segment.In order to observe dynamic express ofβ1-adrenoceptor and M2-muscarinic acetylcholine receptor in MS,semiquantitative analysis was applied to examine the expression of two protein in myocardial tissue of different groups.Results:(1) It is a successful sign of block when left artrium anterior wall become cyanosis and sync-electrocardiogram indicate that S-T segment rise,QRS amplitude is heighten.The cyanosis of left artrium anterior wall is disappeared and S-T segment and QRS become normal after reperfusion.(2) Reperfusion after block the LAD 15 min,we found there is symbiosis between the expression ofβ1-AR and time.β1-AR expression was increased and peaked on 1 hour after reperfusion,compared with control group and experimental group(P<0.05),then gradully decreased and recovered on 72 hours after reperfusion.M2-AChR expression was decreased to a minimum on 4 hours after reperfusion,compared with control group and experimental group(P<0.05),then gradully rising and peaked on 8 hours after reperfusion,compared with control group,1hour,4 hours after reperfusion(P<0.05);lowed on 24 hours after reperfusion;increased again on 72 hours after reperfusion,compared with control group,1hour,4hours,24 hours after reperfusion(P<0.05).The content ofβ1—AR and M2—AchR are different,the later is higher.Conclusion:(1)The model of MS can be established successfully in SD rats.(2)β1-AR and M2-AchR may play an important role in the pathophysiology of MS.
Keywords/Search Tags:Myocardial Stunning, β1-Adrenoceptor, M2-muscarinic Acetylcholine Receptor
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