| Backgroud:Ischemia reperfusion injury is an important pathophysiologic phenomenon during the perioperative time, especially for some emergency time. Restoring its perfusion and oxygenation timely is an effective manner for treating and rescuing. However, after the reperfusion, the injury is more serious, more durable, directly endangered the whole body.Cardiovascular disease is the leading cause of death in the world. Myocardial ischemia reperfusion injury prompts a release of oxygen free radicals, accumulation of inflammatory reaction and over-expression of apoptosis factor. Myocardial ischemia reperfusion injury not only lead to cardiac dysfunction but also may cause distant organ dysfunction, which can increase the morbidity and mortality of patients. The brain is the largest organ of oxygen consumption, which is also unable to carry on anaerobic respiratory, once the hypoxia occurred, the damage is more than other organs. The brain injury caused by myocardial ischemia reperfusion may ever worsen for the survivaling patients, because of lowering their quality of life. Ischemia reperfusion injury is an inflammation. Inflammation is a physiological function of the body repairing necrotic tissue, maintaining defense. What is more, the excessive inflammatory reaction will lead to organs damage. Ischemic preconditioning and ischemic postconditioning has confirmed has the effect of reducing ischemia reperfusion injury through the PTEN/PI-3K/Akt/GSK-3? signaling pathway. As an important molecule, GSK-3? through mPTP channel to regulate cell survivalling. Therefore the signal pathway of brain injury induced by myocardial ischemia reperfusion, the inflammation factor of brain injury induced by myocardial ischemia reperfusion and the protective effects of ischemic postconditioning is a hotly highlights in scientific research.Part One:To establish the model of brain injury induced by myocardial ischemia reperfusion and the protective effect of ischemic postconditioningObjective:To investigate the effect of brain injury induced by myocardial ischemia reperfusion and the function of ischemic postconditioning.Methods:30 SD rats were allocated into 3 groups, group sham (group NS)?group myocardial ischemia reperfusion (group NIR)?group ischemic postconditioning (group NIPost). Myocardial ischemia reperfusion was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. Ischemic postconditioning received 3 cycles of 10 s reperfusion followed by 10 s ischemia at the end of 30 min myocardial ischemia. The brain was immediately removed for determination of histopathology, apoptosis factor, TUNEL.Results:Group NIR significantly increased the number of apoptotic neuronal, down-regulated Bcl-2 expression and up-regulated Bax, Caspase-3 expression as compared with group NS (P<0.01). Group NIPost decreased the number of apoptotic neuronal, up-egulated Bcl-2 expression and down-regulated Bax, Caspase-3 expression ascompared with group NIR (P<0.01).Conclusions:Myocardial ischemia reperfusion can lead to brain injury, ischemic postconditioning has a protective effect on brain injury induced by myocardial ischemia reperfusion.Part Two:The effect of GSK-3? on brain injury induced by myocardial ischemia reperfusion injury and the protective effect of ischemic postconditioningObjective:To investigate the effect of GSK-3? on brain injury induced by myocardial ischemia reperfusion injury and the protective effect of ischemic postconditioning.Methods:40 SD rats were allocated into 4 groups, group sham (group NS)?group myocardial ischemia reperfusion (group NIR)?group ischemic postconditioning (group NIPost)?group ischemic postconditioning+GSK-3? inhibitor (group NIPostI). Inhibitor peritoneal injected 10min before the operation. Myocardial ischemia reperfusion was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. Ischemic postconditioning received 3 cycles of 10 s reperfusion followed by 10 s ischemia at the end of 30 min myocardial ischemia. The brain was immediately removed for determination of histopathology, inflammatory factor, apoptosis factor, TUNEL and western blotting.Results:During the period of myocardial ischemia reperfusion, the structure of brain was damaged seriously. The cytoplasm was light red with uneven distribution and the vacuoles, nuclei were condensed. The expressions of Bax, IL-6, IL-8, TUNEL and cleaved caspase-3 in the brain were significantly increased, while the expressions of Bcl-2, IL-10 and p-GSK-3? were decreased in the group of myocardial ischemia reperfusion. Ischemic postconditioning effectively reversed these changes in protein expression. GSK-3? inhibitor can attenuated the protection.Conclusions:Myocardial ischemia reperfusion can lead to brain injury, ischemic postconditioning has a protective effect on brain injury induced by myocardial ischemia reperfusion by increasing the p-GSK-3?.Inhibitor can eliminate the protective effect-Part Three:The effect of GSK-3p on brain injury induced by myocardial ischemia reperfusion injury in diabetes mellitus and the protective effect of ischemic postconditioningObjective:To investigate the effect of GSK-3? on brain injury induced by myocardial ischemia reperfusion injury in diabetes mellitus and the protective effect of ischemic postconditioning.Methods:40 SD rats were allocated into 4 groups, group sham (group DS)?group myocardial ischemia reperfusion (group DIR)?group ischemic postconditioning (group DIPost)?group ischemic postconditioning+GSK-3?inhibitor (group DIPostI). Diabetes mellitus was induced by intraperitoneal streptozotocin. Myocardial ischemia reperfusion was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. Ischemic postconditioning received 3 cycles of 10 s reperfusion followed by 10 s ischemia at the end of 30 min myocardial ischemia. Inhibitor peritoneal injected 10min before the operation. The brain was immediately removed for determination of histopathology, apoptosis factor, inflammatory factor, TUNEL and western blotting.Results:During the period of myocardial ischemia reperfusion, the structure of brain was damaged more seriously. The cytoplasm was light red with uneven distribution and the vacuoles, nuclei were condensed. The expressions of Bax, IL-6, IL-8, TUNEL and cleaved caspase-3 in the brain were significantly increased, while the expressions of Bcl-2, IL-10 and p-GSK-3? were decreased in the group of myocardial ischemia reperfusion. Ischemic postconditioning partly reversed these changes in protein expression. GSK-3? inhibitor can attenuated the protection.Conclusions:diabetes mellitus can aggravate brain injury induced by myocardial ischemia reperfusion, ischemic postconditioning partly reduce the protective effect on brain injury induced by myocardial ischemia reperfusion by increasing the p-GSK-3?. Inhibitor can eliminate the protective effect. |
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