The Investigation Of Protection Mechanism For Hypoxia Preconditioning To Transient Focal Cerebral Ischemia In Rats

BackgroundCerebrovascular diseases(CVD) have damaged peoples' health. They have high fatality rate and high mutilation rate. About 70% cases in CVDs are ischemic cerebrovascular diseases(ICVD). In recent years, with much mechanism of ICVD has been found, the treatment for it has make a progress. But mechanism of ICVD is not very clear and there's no effective method for it's prevention and cure. In this field emphasis of the research are priming endogenous protection and finding effective treatment. Investigation discovered that hypoxia preconditioning can relieve the brain damage for the next severe ischemia. It's called ischemia tolerance phenomenon. The main respect for ischemia tolerance phenomenon is creating different cerebral ischemia tolerance model in different animals. Because the resemblance between the cerebral vessels and human's, many researchers in the world creating the rat middle cerebral artery occlusion(MCAO) model in different ways. MCAO model created by carotis interna artery embolization has becoming one of the most valuable implement in cerebral ischemia pathomechanism pharmacological experiment for it's simple and effective. This investigation created the MCAO model by refining the Zea Longa thread embolism. Some rats were done hypoxia preconditioning 48h before creating the MCAO model. The rats were tested nerve function, cerebral infarctin volume, cerebral edema degree and hypoxic inducible factor-1α(HIF-1α) to research the protection mechanism for hypoxia preconditioning to transient focal cerebral ischemia.Methods1. Rat group: 130 adult SD rats were separated into 3 groups, sham operation group(10 rats), ischemia reperfusion group(60 rats) and hypoxia precondition +ischemia reperfusion group(60 rats).2. Rats in hypoxia precondition+ischemia reperfusion group were made HP model by Vannucci.R.C method.3. Rats in ischemia reperfusion group and hypoxia precondition+ ischemia reperfusion group were made MCAO model by Zea longa method. Rats in sham operation group were operated with no embolism.4. Rats in each group were tested nerve function, cerebral infarctin volume, cerebral edema degree and hypoxic inducible factor-1α(HIF-1α) in different time point.Results1. The nerve functional disturbance in HP+ischemia reperfusion group was less than ischemia reperfusion group. Ischemic side brain tissue moisture capacity in HP+ischemia reperfusion group was fewer than ischemia reperfusion group. In 24h and 48h time point, ischemic side cerebral infarctin volume in HP+ischemia reperfusion group was less than ischemia reperfusion group.2. HIF-1 protein expression indicated that at 2h time point HP + ischemia reperfusion group was higher than ischemia reperfusion group. This tendency continued to 48h time point. At the same point, HIF-1 protein expression in HP + ischemia reperfusion group was significant stronger than that in ischemia reperfusion group (p<0.05).Conclusion1. Hypoxia preconditioning can increase brain's tolerance to transient focal cerebral ischemia and ameliorate the nerve function by ischemia. 2. Hypoxia preconditioning induced transient focal cerebral ischemia tolerance is probably related to lessening cerebral oedema and stabilization cell function.3. Hypoxia preconditioning induced transient focal cerebral ischemia tolerance is probably related to increasing HIF-1 protein expression.