Objective To investigate the delayed alteration of hippocampus proteome after an-esthesia with isoflurane in aduh and aged rats. Methods Ten 8-month-old SD rats were randomly divided into group Caduh and group Iadult (5 in each group) , and another ten 22-month-old SD rats were randomly divided into group Caged and group Iaged (5 in each group). The rats in group Iadult and group Iaged received 2 h anesthesia with 1.2 % isoflurane. The rats in group Cadult and group Caged inhaled 40% oxygen for contrast. The hippocampal proteome of each rat was measured by 2-dimensional gel electrophoresis and mass spectrometry. Results The vital signs of the rats in group Iadult and group Iaged were stable. There were 878±34 protein spots in group Cadult, 864±49 protein spots in group Iadult, 834±47 in group Caged, and 819±24 in group Iaged. There were 12 (4/8)different protein spots between group Iadult and group Cadult. There were 11 (3/8) different protein spots between group Iaged and group Caged. All of the protein spots were identified by MALDI-TOF-MS. Most of the different proteins were related to metabolism, anti-oxidation, and signal conditioning of synapse. Conclusion Isoflurane may cause the alteration of hippocampal pro-teome in rats, which is age-related.

ObjectiveTo investigate the effects of isoflurane anesthesia on hippocampus synaptosomes proteome in aged rats.MethodsTwenty-seven 22- month-old SD rats weighing 480-550 g were randomly divided into 2 groups: control group (group C,n =6) and isoflurane group (group Ⅰ,n =21 ).In group C inhaled mixed gas containing 80％ oxygen for 2 h.In group Ⅰ the animals were endotracheal intubated after induction by 3％ isoflurane and inhaled 2％ isoflurane and 80％ oxygen for 2 h.Cognition function was evaluated by Y-maze at 24 h after anesthesia and the total training times were recorded.The total training times ＞ 75 was defined as cognitive dysfuction.In group Ⅰ the animals were divided into cognitive dysfuction group (group ⅠA) and non-cognitive dysfuction group (group IB) according to the results of Y-maze test.The animals were sacrificed and their hippocampi were removed and synaptosomes were extracted for two-dimensional gel electrophoresis.The different protein spots were analyzed by mass chromatographic analysis.ResultsSix rats had cognitive dysfuction (group IA) and another thirteen rats had no cognitive dysfuction (group IB).The total training times were significantly higher in group IA than in groups C and IB( P ＜ 0.05).There was no significant difference in the total training times between groups C and IB (P ＞ 0.05).There were 21 (11/10) different protein spots between groups IB and IA,and 19 (12/7) different protein spots between groups C and IA.Thirty-one protein spots were identified by means of MALDI-TOF-MS.ConclusionThe cognitive dysfuction after isoflurane anesthesia in aged rats may be related to the changes of energy metabolism protein,cytoskeletal structure and regulatory protein in synapse of hippocampus.

ObjectiveTo investigate the effects of dexmedetomidine on postoperative cognitive function and monocytes Toll-like receptor 2 (TLR2)and TLR 4 expression in elderly patients.MethodsForty-five ASA Ⅰ or Ⅱ elderly patients aged ≥65 yr weighing 53-72 kg were randomly divided into 3 groups: control group (group Ⅰ ) and different doses of dexmedetomidine groups(groups Ⅱ and Ⅲ ).Dexmedetomidine 1.0 μg/kg was injected iv over 15 min after anesthesia induction,and then was infused at a rate of 0.5 μg·kg-1 ·h-1 (group Ⅱ ) or 1.0 μg· kg-1 ·h-1 (group Ⅲ ) untile the end of operation.Group Ⅰ received equal volume of normal saline.Blood samples were taken before anesthesia induction,at 1.5 h after the beginning of operation,at the end of operation and at 24 h after operation(T,-T5 ) for determination of monocytes TLR2 and TLR4 expression by flow cytometrybased method.Postoperative cognitive function was evaluated at 1 d before and 7 d after operation with Mini-mental state examination and Wechsler memory scale and Wechsler adult intelligence scale,and the postoperative cognitive dysfunction was recorded.ResultsThe incidence of postoperative cognitive dysfunction and monocytes TLR2 and TLR4 expression were significantly lower in groups Ⅱ and Ⅲ than in group Ⅰ,and in group Ⅲ than in group Ⅱ (P ＜ 0.05).ConclusionDexmedetomidine can prevent postoperative cognitive dysfunction in elderly patients,and the mechanism may be related to down-regulation of monocytes TLR2 and TLR4 expression.

Objective To investigate the role of opioid receptors in the protective effects of isoflurane-induced delayed preconditioning against myocardial ischemia-reperfusion (I/R) injury in rabbits. Methods Forty male New Zealand white rabbits weighing 2.0-2.5 kg were randomly assigned into 4 groups ( n = 10 each) : group I sham operation (S); group II I/R; group Ⅲ isoflurane + I/R (Iso) and group IV Iso + naloxone + I/R (Nal). Myocardial I/R was induced by 40 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 120 min reperfusion. In group Ⅲ (Iso) 2% isoflurane in 100% O2 was inhaled for 2 h and I/R was produced 24 h later. In group IV (Nal) naloxone 6 mg/kg was given iv 10 min before 2 h of 2% isoflurane inhalation and I/R was produced 24 h later. At the end of 120 min reperfusion, infarct size (IS) and area at risk (AAR) were determined by Evan's blue and TTC staining. Myocardial ultrastructure was examined by electron microscopy. The phosphorylated p38MAPK protein expression in myocardium was determined by Western blot. Results The IS was significantly smaller in group Iso ( Ⅲ ) ( 19.7% ± 2.8%) than in I/R group ( II ) (37.8% ±1.7%) (P<0.05). The phosphorylated p38MAPK protein expression in myocardium was significantly lower in group Iso than in group I/R. Microscopic examination showed less myocardial damage in Iso group than in group I/R. The protective effects of delayed preconditioning by isoflurane was prevented by naloxone pretreatment. ConclusionOpioid receptors may be involved in the protective effects of delayed preconditioning by isoflurane against myocardial I/R injury.

Objective To investigate the effects of isoflurane delayed preconditioning(IDP) on myocardial proteomin rabbits with myocardial ischemia-reperfuaion(I/R).mjury.Methods Eight New Zealand white rabbits of both sexes weighing 2.0-2.5 kg were randomly divided into 2 groups(n=4 each):I/R group and IDP group.Myocardial I/R Wgg induced by occlusion of left anterior descending artery for 40 min followed by 120 min repednsion.In group IDP.the animals inhaled 2%isoflurane for 2 h,undergoing I/R 24 h later.At the end of 120 min reperfusion,the myocardium of left ventricle anterior wall was removed for two-dimensional gel electrophorvsis.The different protein spots were analyzed by means of mass chromatography.Results There were 13 different protein spots between group I/R and IDP.Of the 13 proteins,the expression of 10 spots Was up-regulated and 3 spots down-regulated in quantity.Eleven protein spots of all spots were identified by means of MALDI-TOF-MS.Conclusion IDP can aNenuate myocardial I/R injury in rabbits and it may be related to the alteration in proteome of myocardium.

Objective To explore the mechanism of the catdioprotection of isoflurane delayed preconditioning on myocardial ischemia reperfusion injury in rabbits.Method Thirty male New Zealand white rabbits,weighing 2.0 to 2.5 kg,were randomly divided into three groups(ten for each group):Control group(group C),I/R group(I/R group) ,2.0% isoflurane group(group S) .Group S was exposed to 2.0% isoflurane-100% oxygen for2 h.Group C and I/R group were exposed 2 h to 100% oxygen served as untreated controls.Twenty-four hours later I/R group and group S underwent 40 rain of coronary occlusion followed by 2 h of reperfusion.Blood samples were taken from arterial line at 20 min before occlusion(T1) ,20 rain after occlusion(T2) ,40 rain after occlusion(T3) ,1 h after reperfusion(T4) and 2 h after reperfusion(TS) for determination of plasma IL-10 levels and TNF-alevels by ELISA.At the end of the reperfusion,infarct size and area at risk were defined by Evans and TTC staining.The heart was harvested and levels of the nuclear factor kappa β(NF-κB)activity were determined by Western Blot,and ultrastructures were observed by electron microscopy.The data was expressed as,and were analyzed by using oneway ANOVA test with SPSS 13.0.P value less than 0.05 indicated statistical significance.Results The NF-κB activity of group S was significantly lower than that of group I/R(P<0.05).Group S significantly(P<0.05)reduced infarct size(19.7%±2.8% in group S) of the left ventricular area at risk as compared with control (37.8 %±1.7 % in I/R group).The injury of I/R group was worse than that of group S from the changes of the cellular structure under light microscope.Group S had a lower levels of TNF-α and also had a higher level of IL-10.Conclusions Isoflurane can inhibit NF-κB activity during myocardial ischemia reperfusion and modulate the cytokine expression,which may be one of molecular mechanisms of Isoflurane delayed preconditioning on cardioprotection.

Objective To study the correlations between the genetic polymorphism of brain-derived neurotrophic factor (BDNF) and the postpartum depression (PPD) in cesarean section parturient. Methods Three hundred and sixty parturients, who underwent cesarean section under spinal anesthesia from Feb. 2014 to Feb. 2015 in Third Xiangya Hospital of Central South University or Hunan Maternal and Child Health Hospital, were selected as subjects. The general information of parturients was recorded and Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate the depression condition of parturients at the prenatal 1 day and the 42th day postpartum, and with a cut-off point of 12/13 for identifying PPD. The genotypes of BDNF gene locus G712A, rs56164415, rs11030100, rs11030101 and rs6265 were measured by Sequenom? Mass Array SNP. Finally, the correlations of PPD to different genotypes and general information of parturients were statistically analyzed. Results The incidence of PPD among the selected subjects was 7.2%. Pregnancy mental stress, poor pregnancy mood, perinatal elevated monocyte count, prenatal depression mood and BDNF gene locus rs6265 mutation all could affect the incidence of PPD in cesarean section parturients (P<0.05). No statistically significant difference existed between BDNF gene G712A, rs11030101, rs11030100 and rs56164415 locus mutation and PPD (P>0.05), and their haploid forms were not related to PPD also. Conclusion BDNF rs6265CC genotype, pregnancy mental stress, poor pregnancy mood, perinatal elevated monocyte count and prenatal depression mood are the risk factors for postpartum depression.

Objective To evaluate the influence of epimeric glycyrrhizic acid on production of endothelin-1 (ET-1) in the lungs induced by ischemia-reperfusion(I/R) injury.Methods Twenty healthy long-ear white rabbits of both sexes, weighing 1.1-2.1kg were randomly divided into 2 groups: group I I/R alone ( n = 10) and group II I/R + epimeric glycyrrhizic acid (n = 10). The animals were anesthetized with thiopental 25 mg?kg-1 and tracheotomized and mechanically ventilated (FiO2 = 100% , VT = 10-13 ml?kg, RR = 20-30 bpm, I:E= 1: 1.2). Anesthesia was maintained with fentanyl, thiopental and vecuronium. Femoral artery was cannulated for continuous direct BP monitoring. MAP was maintained at 70-90 mm Hg during experiment. Right interval jugular vein was cannulated. Catheter was inserted into right atrium for fluid administration, blood sampling and right atrial pressure monitoring. Chest was opened and the hilum of right lung was mass-ligated to induce ischemia for 60 min and then released for reperfusion for 60 min. Epimeric glycyrrhizic acid 30 mg?kg-1 was given iv 30 min before ischemia of the right lung. Blood samples were taken from right atrium and femoral artery for determination of ET-1 concentration before ischemia of right lung (T0) and 1 and 5 min after right lung started being perfused (T1 , T2). At the end of 60 min reperfusion of the right lung, the animals were sacrificed and lungs (right and left) were removed for electron microscopic examination. Results In group 1 at T, the ET-1 levels in the blood from both femoral artery and right atrium were significantly higher than the baseline (T0) and the ET-1 concentration in the blood from femoral artery was significantly higher than that from right atrium. In group II there was no significant difference in blood ET-1 concentration between T0 and T, .Conclusion Ischemia-reperfusion induces increased production of ET-1 in the injured lung. Epimeric glycyrrhizic acid can inhibit the increase in the production of ET-1 in the induced by I/R.

Objective To investigate the changes in cerebral glucose metabolism induced by postoperative delirium in the elderly patients and the effects of dexmedetomidine on it.Methods Forty-two patients of both sexes aged 65-85 yr with a body mass index of 19-25 kg/m2 undergoing abdominal surgery under general anesthesia were enrolled in this study.Delirium occurred during the first 2 days after operation in 39 out of the 42 patients (29/42).The 29 patients were randomly divided into 2 groups:group delirium without any treatment (group D,n =13) and group delirium + dexmedetomidine (group Dex,n =16).The remaining 13 patients did not develop delirium after operation and served as control group (group C).In group Dex a loading dose of dexmedetomidine 1 μg/kg was administered iv over 10 min after occurrence of delirium followed by continuous infusion at 0.2-0.7μg· kg-1 · h-1.PET scan was performed within the time period in which delirium occurred.18 Fluorine-deoxyglucose was injected for observation of imaging of glucose metabolism.The standard uptake value of glucose of bilateral parietal,temporal and frontal lobes was calculated.Results Delirium was controlled within 30 min after adminnistration of dexmedetomidine.Delirium significantly reduced cerebral glucose metabolism in the bilateral parietal,temporal and frontal lobes in group D as compared with group C (P ＜ 0.05).Dexmedetomidine significantly attenuated the delirium-induced decrease in cerebral glucose metabolic rate of the 3 lobes in group Dex as compared with group D (P ＜ 0.05).Conclusion Postoperative delirium reduces cerebral glucose metabolism and dexmedetomidine can significantly control pastoperative delirium in the elderly patients.

Objective To evaluate the effect of MDR1 gene polymorphisms on the neuromuscular block of rocuronium. Methods One hundred thirty-five patients, aged 18-50 yr, with body mass index of 18-25 kg∕m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing gynecologic laparoscopic operation under general anesthesia, were enrolled in the study. Anesthesia was induced with midazolam 006 mg∕kg, sufentanil 07 μg∕kg, propofol(target plasma concentration 6 μg∕ml)and remifentanil(target plasma concentration 6 ng∕ml). After the patients lost consciousness, neuromuscular block was assessed with TOF-Watch SX accelerometer, and rocuronium 06 mg∕kg was intravenously injec-ted. Anesthesia was maintained by target-controlled infusion of propofol(target plasma concentration 3-5 μg∕ml)and remifentanil(target plasma concentration 3-6 ng∕ml). Rocuronium 015 mg∕kg was added when T1reached 25% of control. The onset time of rocuronium, maintenance time of induction dose, main-tenance time of additional dose and recovery index were recorded. Peripheral venous blood samples were collected for MDR1 genotype(MDR1 1236 C>T and 3435 C>T)analysis using polymerase chain reaction-restriction fragment length polymorphism. Results For MDR1 1236 C>T genotype, there were 19 cases of MDR1 1236 CC genotype, 72 cases of MDR1 1236 TT genotype, 44 cases of MDR1 1236 CT genotype. Compared with patients of MDR1 1236 CC, the maintenance time of induction dose, maintenance time of additional dose and recovery index were significantly prolonged in patients of MDR1 1236 TT and CT geno-types(P<005). For MDR1 3435 C>T genotype, there were 58 cases of MDR1 3435 CC genotype, 55 cases of MDR1 3435 TT genotype, 22 cases of MDR1 3435 TC genotype. There was no significant differ-ence in maintenance time of induction dose, maintenance time of additional dose and recovery index among patients of different MDR1 3435 C>T genotypes(P>005). Conclusion MDR1 1236 C>T gene poly-morphisms affects the neuromuscular block of rocuronium, and the genetic factor may be one of the reasons contributing to the individual variation in the efficacy.