| The mortality caused by trauma increased year by year and hemorrhage shock tops the list of traumatic death.Hemorrhage shock is acute circulatory failure due to blood loss,it is a critical systemic pathological process.Hemorrhage shock results in inadequate organ perfusion and tissue oxygenation.Brain tissue,especially hippocampus is more sensitive to ischemia and hypoxia.Although fluid resuscitation is the primary resuce treatment of the hemorrhage shock,it can induce ischemia and reperfusion injury,such as cerebral ischemia and reperfusion injury,which may aggravate the injury of hippocampal neurons,leading to cognitive dysfunction in patients.Sevoflurane,as a novel volatile anesthetic with minimal pungency,fast onset,is widely used in clinical anesthesia.Accumulating studies have demonstrated that postconditioning with sevoflurane has neuroprotection under cerebral ischemia and reperfusion injury.In our study,we made a hemorrhage shock and resuscitation model to investigated whether sevoflurane postconditioning exert neuroprotection and its mechanism.Experiment 1.Sevoflurane postconditioning could ameliorate the ability of spatial learning and memory after hemorrhage shock and resuscitation in rats and its effect on cholinergic neurons in hippocampusObjective To investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats and if its mechanism involving the protection of cholinergic neurons in hippocampus.Methods Adult male Sprague-Dawley rats,weighing 300-350 g,were randomly allocated to 5 groups(n=8): sham group(sham),hemorrhage shock and resuscitation group(shock),low concentration(sevo1,1.2%),middle concentration(sevo2,2.4%)and high concentration(sevo3,3.6%)of sevoflurane postconditioning groups.Hemorrhage shock and resuscitation was induced by the withdrawn of 40% of the total blood volume from the right carotid artery over an interval of 30 min,one hour after finishing the bleeding,and received an infusion of the blood over 30 min.Sevoflurane postconditioning groups were treated with the concentrations of 1.2%,2.4% and 3.6%sevoflurane respectively at the onset of reperfusion.Mean arterial pressure was recorded at a 10-min interval.Artery blood samples were withdrawn before withdrawing blood(T0),30 min after bleeding(T1),before infusion of the blood(T2),and after reinfusion(T3)for blood gas analysis.The spatial learning and memory ability of the rats were measured by Morris water maze 72 h after reinfusion.Then the animals were sacrificed,brains were removed,and the morphology of hippocampal CA1 region was observed by H &E staining.The expression of choline acetyltransferase(CHAT)and acetylcholinesterase(ACHE)in the hippocampus CA1 region was detected by immunohistochemistry.Results Compared with sham group,mean arterial pressure in T1-T2 was significantly decreased(P<0.05)in the other four groups,Arterial lactic acid was significantly increased at T1 and T2 in the shock,sevo1,sevo2,and sevo3 groups(P < 0.05),while The BE,PH,HB,and PCO2 were all significantly reduced at T1 and T2.Compared with sham group,the latency was significantly increased,while the swimming distance and the proportion of time spent in target quadrant were decreased in the shock and sevo1 groups.There was a large number of necrotic neurons in the hippocampal CA1 region,and the expression of CHAT was significantly decreased while the expression of ACHE increased in the shock and sevo1 groups compared with sham group(P<0.05).Sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability,declined the necrosis of neurons in the hippocampal CA1 area,increased the expression of CHAT and decreased the expression of ACHE in hippocampal CA1 region when compared with shock group(P <0.05).Conclusion Postconditioning with sevoflurane at the concentrations of 2.4% and 3.6%could improve the spatial learning and memory abilit in hemorrhage shock and resuscitation rats,which maybe correlate with the protection of hippocampal CA1 cholinergic neuron.Experiment 2.Postconditioning with sevoflurane ameliorates spatial learning and memory deficit by attenuating endoplasmic reticulum stress-induced apoptosis in hemorrhage shock and resuscitation rats in hippocampusObjective To investigate whether sevoflurane postconditioning could improve spatial learning and memory ability by suppressing ER stress-induced apoptosis in rats with hemorrhage shock and resuscitation.Methods Adult male Sprague-Dawley rats,weighing 300-350 g,were randomly divided into 3 groups(n=12): sham group(sham),hemorrhage shock and resuscitation group(shock),sevoflurane postconditioning groups(SP).The establishment of the model and the treatment of sevoflurane postconditioning were identical with the experimental one.Mean arterial pressure was recorded at a 10-min interval.Artery blood samples were withdrawn before withdrawing blood(T0),30 min after bleeding(T1),before infusion of the blood(T2),and after reinfusion(T3)for blood gas analysis.6 rats of each group were selected to detect spatial learning and memory ability by Morris water maze 3days after reinfusion.Then the animals were sacrificed,brains were removed,and we detected the apoptosis of neurons in hippocampal CA1 area using the Terminal-deoxynucleoitidl Transferase Mediated Nick End Labeling(TUNEL)method.The hippocampus of the rest 6 rats in each group was isolated to detect the expression of GRP78 and CHOP by western blot at the 72 h after resuscitation.Results Compared with the sham group,mean arterial pressure was significantly decreased(P<0.05),the blood lactic acid was significantly increased at T1-T2 in the shock and SP groups(P<0.05),the latency,the number of apoptotic cells in hippocampal CA1 area and the expression of CHOP and GRP78 in the hippocampal tissues were significantly increased in the shock group while the swimming distance and the proportion of time spent in the target quadrant were decreased(P<0.05).Compared with the shock group,the latency,the number of apoptotic cells and the expression of CHOP and GRP78 were significantly declined in the SP group while the swimming distance and the proportion of time spent in the target quadrant were significantly increased.Conclusion Sevoflurane postconditioning with the concentration of 2.4% could improve the spatial learning and memory ability in rats following hemorrhage shock and resuscitation rats,which maybe correlate with reducing neuronal apoptosis and suppressing endoplasmic reticulum stress.Conclusions1.Postcontitioning with sevoflurane could ameliorate spatial learning and memory ability in rats with hemorrhage shock and resuscitation and the effect is dose dependent.2.Sevoflurane postconditioning could improve the spatial learning and memory abilit in hemorrhage shock and resuscitation rats,which maybe correlate with the protection of hippocampal CA1 cholinergic neuron.3.Sevoflurane postconditioning could inhibit the apoptosis of hippocampal neurons induced by endoplasmic reticulum stress in rats with hemorrhage shock and resuscitation. |
PDF Full Text Request