| ObjectivePatients have to go through the ischemia-reperfusion process during the cardiopulmonary bypass surgery.Some patients are satisfied with their heart pathological changes correction,but their heart function may also be decreased or even failure after the operation,which will seriously affect the disease treatment.Effective myocardial protection has always been the focus of clinical research.Rho kinase, combined with small GTP and important RhoA protein effector molecules are important effectors,are important enzyme which participated in a series of cell biosis such as cell mitotic adhesion,cytoskeletal adjustment,muscle cell contraction and tumor cell infiltration.Rho/Rho kinase signaling pathway are directly bound up with some major cardiovascular disease such as hypertension,heart failure,myocardial infarction and atherosclerosis.The pathogenesis of myocardial ischemia-reperfusion injury relates to Rho/Rho kinase signaling pathway,while it is reported in document that Rho-kinase inhibitor provides protective action on myocardial ischemia-reperfusion injury.Rho/Rho kinase signaling pathway involves in the regulation of vascular smooth muscle calcium and myocardial cells sensitivity,the high expression of Rho-kinase may increase Ca2+ sensitivity in smooth muscle cells to cause smooth muscle contraction,which can lead to coronary spasm and aggravate myocardial damage,but meanwhile the high expression of Rho-kinase may also increase the calcium sensitivity of myocardial cells to increase myocardial contractility and improve cardiac function.Therefore,this study,applies rat heart in vtro Langendorff model,studies effects of Rho-kinase on rat heart ischemia-reperfusion injury through the application of Rho-kinase inhibitor fasudil and agonists Ang-Ⅱ.MethodDivided 60 healthy SD rats,weighing 220-320g into 6 groups randomly:(A) normal control group,(B) ROCK agonist normal group,(C) ROCK inhibitor normal group,(D) ischemia-reperfusion control group,(E) ischemia-reperfusion ROCK inhibitor group,(F) ischemia-reperfusion ROCK agonist group.Use Langendorff in vitro heart as a model,after 10 minutes s' KH-liquid equilibrium,pour K-H liquid into group A for another 70 minutes;continuously add ang-Ⅱ0.36μg/kg to group B for 10 minutes s after 70 minutes' reperfusion;continuously add fasudil 0.4mg/kg for 10 minutes s to group C after 70 minutes' perfusion;in group D ischemia 30 minutes later,reperfuse 40 minutes;continuously add fasudil 0.4mg/kg for 10 minutes after 30 minutes' reperfusion in Group E;continuously add ang-Ⅱ0.36μg/kg for 10 minutes to Group F after 30 minutes' reperfusion,then detect left ventricular contraction function and coronary blood flow separately while the perfusion are in process at 10 minutes,60 minutes,70 minutes and 80 minutes,use Western blot detection to find the Rho-kinase protein expression at the end of reperfusion.ResultsAfter adding ang-Ⅱto Group B,the LVSP increased,LVEDP increased,+dP/dt increased,heart rate decreased,coronary blood flow decreased,ROCK expression increased,which is differet from group A(p＜0.05);has no difference with group C,which every target is stable at any time point(P＞0.05);after ischemia-reperfusion, group D,E,F have following phenomenon:LVSP reduced,LVEDP increased,+dP/ dt reduced,coronary blood flow decreased,ROCK expression increased,different from the control group(p＜0.05);among them,before drug treatment,the target remain the same for group E and group F(P＞0.05);Group F's LVSP is higher than Group E after drug treatment,as well as the LVEDP,+dP/dt and ROCK expression,in contrary, group F's coronary blood flow is lower than group E,statistic difference(p＜0.05). while adding ang-Ⅱto group F,there's 50%possibility of cardiac arrest or ventricular fibrillation.ConclusionThe expression of ROCK activity increased in myocardial ischemia-reperfusion injury,ROCK agonist ang-Ⅱcan increase ROCK activity and may improve the cardiac systolic function in short-term after the ischemia-reperfusion injury,but at the same time it can also accentuate myocardial ischemia and hypoxia caused by coronary artery spasm,make the myocardial injury heavier,Rho kinase inhibitor fasudil has a protective effect on myocardial injury caused by ischemia-reperfusion.
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