Change And Significance Of Expression Of InsR And IGF-1 On Ischemia-reperfusion Myocardial Insulin Resistance In Dog During Cardiopulmonary Bypass

Objective: To observe the expression of insulin receptor(InsR) protein content and total gene and, insulin-like growth factor l(IGF-l) during myocardial ischemia-reperfusion in dog with cardiopulmonary bypass, and discuss their significance. Methods: Twelve healthy mongrel dogs are randomly divided into two groups. Group 1 (n=6) received aortic cross-clamping for 30 mins and Group 2 (n=6) received aortic cross-clamping for 120 mins. Blood samples of coronary sinus and coronary artery at pre-bypass, aortic cross-clamp off at 15, 45, and 75 mins, espectively were detected for glucose, insulin and glucagon, IGF-1 analysis by Radioimmunity, and the biopsy samples from the heart were taken for InsR, IGF-1 analysis by Immunohistochemistry or/and Real Time RT-PCR, some of them was detected for glycogen analysis by Anthrone Chromatometry; Meanwhile, the perioperative hemodynamics was monitored. Results: (1). Mcardial glusose metabolism: Plasma glucose increases highly and reaches its peak level at 15 and 45minutes after reperfusion(P<0.01). Meantime, myocardium glycogen decomposition is reinforced obviously, while myocardium glucose uptake/utilization were hindered greatly comparied with group 1 , plasma glucose in group 2 increases more standly and greatly .Net myocardial glucose ingestion and myocardial ingestion ratio descend to zero at 15 minutes after reperfusion during CPB, which are all recovered to some extent from 45 minutes after reperfusion. Compared with group 1, myocardium glucose uptake/utilization are more slow and long-lasting In group 2(P<0.05). (2). Change of plasma insulin, glucagon: After ischemia-reperfusipn, plasma insulin, glucagon are all increased obviously and reach their peak points at 15 minutes, and remaining at high level until 75 minutes after reperfusion. There are obvious discrepancy (P<0.01) than pre-bypass. Compared with group 1, which increase more obviously, and recovery are slower and long-lasting in group 2(P<0.05). (3) Insulin resistance index: Insulin resistance index in two groups increase apparently during CPB, reach their peak points at 15 minutes, and remaining at high level until 75 minutes after reperfusion. There are obvious discrepancy (P<0.01) than pre-bypass. Compared with group 1, which increase more obviously, and recovery are slower and long-lasting in group 2(P<0.05). (4) Change of myocardium InsRα,βprotein conten and total mRNA expression: InsRα,βprotein conten and total mRNA expression all reduce obviously at 15 minutes after ischemia-reperfusion, There are obvious discrepancy (P<0.01) than pre-bypass. Compared with group 1, which decrease are more severely, and recovery are slower and long-lasting in group 2(P<0.05). (5) Change of plasma IGF-1 and myocardium IGF-1 protein content: Plasma IGF-1 and myocardium IGF-1 protein content all reduce obviously at 15 minutes after ischemia-reperfusion, There are obvious discrepancy (P<0.01) than pre-bypass. Compared with group 1, which decrease are more severely, and recovery are slower and long-lasting in group 2(P<0.05). (6) Hemodynamics: Left ventricular systolic pressure( LVSP) and maximal rate of rise of left ventricular pressure(LV dp/dtmax) in two groups all decrease obviously, and left ventricular end-diastolic pressure( LVEDP) increase highlier after reperfusion (P<0.01) and recover slowly later. Comparied with group 1, changing of the LVSP and LV dp/dtmax are more obviously and slower recovery in group 2,(P>0.05). There are obvious discrepancy (P<0.01) than pre-bypass. Conclusions: (1) The decreasing of InsRα,βprotein conten and total mRNA expression may be one of the most important molecular mechanism which causes the myocardium insulin resistance on reperfusion of ischemic myocardium during CPB. The more longer the ischemia lasts, the more obvious the expression of InsR decreases and the more serious the insulin resistance is. (2) IGF-1 may be recognised as one of character of myocardium insulin resistance, the more serious the degree of insulin resistance is, the more obvious the expression of IGF-1 decrease.