| Background：The Incidence of stroke has been high, the high morbidity andmortality rate of stroke impact on people’s health and life, and a heavy financialburden to society. At present, there are no effective drugs to prevention andtreatment of stroke. Ischemic preconditioning-induced ischemic tolerance tobrain provides a new idea for the prevention of stroke. However, it is difficult tobe used in clinic due to the limitations of its methodology. Therefore, there is anurgent necessary to find out a simple and excellent effect to against stroke.Facing this dilemma, we start with the pathogenesis of stroke. Cerebralischemia-reperfusion injury is more serious damage than cerebral ischemia. it isan extremely complex process of physiological and pathological changes,including the ischemia primary injury and secondary damage of the reperfusionperiod. Previous study shows that, cerebral ischemia and reperfusion caused aseries of enzymatic cascade reaction, and the mechanism may be related to theneurotoxicity of excitatory amino acid damage, inflammation, apoptosis, mitochondrial damage, intracellular Ca2+overload, free radical release related.These factors influence each other, build up a complex network structure, andlead to the ischemia and reperfusion injury eventually.Caloric restriction (CR) can extend mean and/or maximum lifespan ofyeast, nematode, rodents and monkeys. It is one of the most effective ways toextend the lifespan. Many health benefits are induced by CR, CR produces thephysilolgic changes, provides protection from type2diabetes,neurodegenerative diseases, and cerebral vascular diseases. It also reduces thebrain infarct size and promotes neurological functional recovery. SIRT1plays animportant role in the biological effects induced by CR. The study found thatknockout mice of SIRT1after CR can not be prolonged life, whileoverexpression of SIRT1in mice can be induced the similar biological activitylike CR. However, the mechanism of CR-induced cerebral ischemic toleranceeffect and the relationship of SIRT1are unclear. Therefore, this experimentfocuses on the relationship of CR induced cerebral protective effects and SIRT1.Objective: It is known that CR induces brain ischemic tolerance, whileassociated mechanism is still unclear. This study investigated the relationshipbetween SIRT1and brain ischemic tolerance induced by CR.Methods: The SD rats which born in the same batch after6weeks normalfeeding were divided into two groups: CR group and AL group. The CR groupwas provided60%energy to intake compared with AL group. Following4weeks of feeding, we detected of body weight and blood glucose of AL rats andCR rats. The middle cerebral artery occlusion (MCAO) was conducted120minand reperfusion24h to induce transient focal ischemic stroke. Then SIRT1levelsin brain were measured via Western Blot and Rt-PCR at3,6,12,24h after MCAO. Double immunofluorescent labeling positioning SIRT1and neurologicfunction scores and infarct volume were assessed24h after reperfusion. Theintra-cerebro-ventricular (i.c.v.) injection of siRNA was administered to downSIRT1and detected infarct volume and neurological function scores after24h ofi.c.v. Observe the relationship between SIRT1and brain ischemic toleranceinduced by CR.Results：①Body weight of CR group were less then AL group (P <0.05);Theblood glucose of CR group compared with AL group were no significantdifference;②Neurologic function score of CR was superior than AL（P<0.05）;The brain infarct volume was improved markedly via CR than AL（P<0.05）;③In comparison with the AL group, CR enhanced the synthesis of SIRT1significantly （P<0.05）, and ameliorated the downregulation of SIRT1expression after6,12h of MCAO （P<0.05）;④siRNA significantlydown-regulated SIRT1at48h after injection, knockdown of SIRT1by siRNA invivo reverses the neuroprotective effect of CR.Conclusion： CR induces brain ischemic tolerance on rats via increasing thesynthesis of SIRT1. |
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