| Cardiac arrest(CA) could make the whole organs ischemia and hypoxia, many patients could restore spontaneous circulation by timely and effective cardiopulmonary resuscitation(CPR). But brain injury after restoration of spontaneous circulation(ROSC)brought pain and the heavy burden to patients and their families. Looking for the feasible measures of brain recovery has become an urgent thing in the world. It has been very many and deep about the neuroprotective research now, but these research seldom were applied to clinical work. In recent years, people found that remote ischemic postconditioning(RIPost) can reduce irreversible tissue injury by a prolonged episode of ischemia/reperfusion(I/R) through a subsequent transient periods of I/R. Because RIPost can be implemented after the ischemia incident happened, it has an important clinical value for the neuroprotection. But the current study focused on focal cerebral I/R injury and 4-vascular method caused to cerebral I/R injury, seldom asphyxial cardiac arrest(ACA) cerebral I/R injury. Janus kinase 2/signal transducer and activator transcription3(JAK2/STAT3) signaling pathway is an important cytokine transduction pathway, widely involved in cell proliferation, differentiation and apoptosis, has closely associated with pathophysiological process of cerebral ischemia. Research has shown that JAK2 / STAT3 signaling pathway may be involved in cerebral I/R injury. But the specific mechanism is still unclear. Thus, the first objective of this study was to investigate whether RIPost could reduce cerebral I/R injury in rats after ACA resuscitation, and further reveals whether JAK2/STAT3 was involved in the neuroprotective effects induced by RIPost in the rat model of ACA.Experiment I Effects of remote ischemic postconditioning on braininjury in rats after asphyxial cardiac arrest resuscitation Objective:To investigate whether RIPost could reduce global cerebral I/R injury in rats after ACA resuscitation.Methods:Sixty-nine adult male SD rats, weighing 300-350 g, were randomly devided into three groups(n=23):Sham operation group(group Sham), asphyxial cardiac arrest resuscitation group(group Control), remote ischemic postconditioning group(group RIPost). CA was induced by 8-min asphyxiation in rats and the animals were resuscitated with a standardized method. After resuscitation, group RIPost was generated by 3 cycles of 15 min occlusion/15 min release of the right hind femoral artery. The survival rate after resuscitation was recorded. NDS, the number of viable hippocampal CA1 neurons were evaluated at 24 h, 72 h or 7days after ROSC. NSE concentration in serum was assessed at48 h after resuscitation. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion.Results:Compared with group Sham, NDS all the time and the number of viable hippocampal CA1 neurons in brain tissue decreased, NSE concentration in serum increased, lantency prolonged, target quadrant residence time percentage and distance percentage decreased in group Control and group RIPost(all P<0.05). Compared with group Control, NDS all the time and the number of viable hippocampal CA1 neurons in brain tissue increased, NSEconcentration in serum decreased, lantency shortoned, target quadrant residence time percentage and distance percentage increased in group RIPost(all P < 0.05). The hippocampal CA1 neuron cells injury in brain tissue in group RIPost were reliever than group Control.Conclusion:RIPost protects the brain against global cerebral I/R injury in rats after asphyxial cardiac arrest resuscitation.Experiment â…¡ The role of JAK2/STAT3 in the neuroprotective effectsinduced by RIPost in a rat model of asphyxial cardiac arrest Objective:To investigate the role of JAK2/STAT3 in the neuroprotective effects induced by RIPost in a rat model of ACA.Methods:Forty adult male SD rats, weighing 300-350 g, were randomly devided into four groups(n=10):Sham operation group(group Sham), asphyxial cardiac arrest resuscitation group(group Control), remote ischemic postconditioning group(group RIPost), remote ischemic postconditioning with the JAK2 inhibitor AG490 group(group AG490). CA was induced by 8-min asphyxiation in rats and the animals were resuscitated with a standardized method. After resuscitation, group RIPost was generated by 3 cycles of 15 min occlusion/15 min release of the right hind femoral artery; group AG490 was generated by 3 cycles of 15 min occlusion/15 min release of the right hind femoral artery and treated with the JAK2 inhibitor AG490. The survival rate after resuscitation was recorded. The number of viable hippocampal CA1 neurons were evaluated at 72 h after ROSC. Expression of Bcl-2, Bax and phosphorylated STAT3(p-STAT3) were detected24 h after ROSC.Results:Compared with group Control, RIPost increased the number of viable hippocampalCA1 neurons, up-regulated the expression of Bcl-2 and p-STAT3, down-regulated the expression of Bax(all P<0.05). Compared with group RIPost, the JAK2 inhibitor AG490 decreased the number of viable hippocampal CA1 neurons, down-regulated the expression of Bcl-2 and p-STAT3, up-regulated the expression of Bax(all P<0.05).Conclusion:JAK2/STAT3 could be involved in the neuroprotective effects induced by RIPost in the rat model of ACA through up-regulating the expression of Bcl-2 and down-regulating the expression of Bax. |
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