Objective To evaluate the effect of intrathecal (IT) NR2B antisense oligonucleotide (aNR2B) on cognitive function in morphine-dependent rats.Methods Male SD rats weighing 230-270 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg/kg.IT catheter was placed at L3-4 interspace according to the technique described by Yang. Thirty rats in which IT catheter was successfully placed without any complication were randomly divided into 3 groups(n=10 each):control group (group C), morphine dependence group (group MD) and group aNR2B.Morphine dependence was induced in group MD and aNR2B by increasing doses of morphine for 6 days. The initial dose of morphine was 10mg/kg injected subcutaneously (SC) twice a day and was increased by 10 mg/kg.every other day.The final dose was 50mg/kg. Then morphine 30 mg/kg was administered SC once a day for 4 weeks. aNR2B 15 nmol was administered IT at 30 min before SC morphine every day in group aNR2B.In control group normal saline was administered instead of morphine. Morris water maze was used to assess the cognitive function at 0 (T0, baseline),1 and 3 weeks of morphine administration (T1,T2).The escape latency and the number of times the animals crossing the plateform were recorded. The animals were killed after the test and the hippocampus was isolated for determination of choline acetytransferase(ChAT)expression.Results There was no significant difference in the baseline escape latency and the baseline number of times the animals crossing the plateform at T0 among the 3 groups. The escape latency was significantly prolonged and the number of times the animals crossing the plateform decreased at T1 and T2 as compared with the baseline at T0 in group MD.The ChAT expression was significantly down-regulated in group MD as compared with control group. IT aNR2B significantly ameliorated cognitive dysfunction at T1 and T2 and increased ChAT expression in group aNR2B compared with group MD.Conclusion IT NR2B antisense oligonucleotide can attenuate cognitive dysfunction through up-regulation of ChAT expression in hippocampus in morphine-dependent rats.

Objective To select the intravenous anesthetic with less effects on the erythrocyte immunity,and observe regulation of ?-endorphin on erythrocyte immunity in vivo Methods Seventy-two mice were randomly allocated to receiving intraperitoneally normal saline 0 04ml/g (group I,n=13), thiopental sodium 60mg/kg (groupⅡ,n=10),etomidate 20mg/kg (groupⅢ,n=10),etomidate -lipuro12mg/kg (groupⅣ n=9), midazolam 20mg/kg (groupⅤ,n=12),fentanyl 100?g/kg (groupⅥ,n=10) or pethidine 20mg/kg (groupⅦ,n=10) at 9 o'clock in the morning ,respectively and were administered at half dosage at 3 o'clock in the afternoon At 9 o'clock of the next day.Results Compared with those in group Ⅰ, the rosette rate of RBC-C3b receptor(RC3bRR) decreased significantly in group Ⅱ, Ⅳ,Ⅴ and Ⅶ(P

ObjectiveTo investigate the effect of infusion of esmolol on expression of hypoxia inducible factor-1α following spinal ischemia-reperfusion (I/R) in rats.MethodsThirty-six healthy male Wistar rats weighing 300-350 g were randomly assigned into 3 groups (n =12 each):group Ⅰ sham operation (group S); group Ⅱ spinal I/R and group Ⅲ esmolol pretreatment (group E).Spinal ischemia was produced by cross-clamping of abdominal aorta distal to renal artery for 20 min in I/R and E groups,Infusion of esmolol 200 g· kg- 1 ·min- 1 was initated 30 min before spinal ischemia and continued for the subsequent 1 h reperfusion in group Ⅲ (E).In groups S and I/R the animals received equal volumes of NS instead of lidocaine.Neurological behavior was assessed according to Tarlov scoring system at 24 and 48 h of reperfusion.The lumbar segment ( L4、5 ) spinal cord was resected at 24 and 48 h ofreperfusion for microscopic examination.The expression of HIF-Ia in spinal cord was detected by immunohistochemistry analysis.ResultsCompared with group S,the expression of HIF-Iα in spinal cord was down-regulated,and Tarlov score was significantly decreased in groups S and l/R.The spinal cord injury was attenuated in group E compared with group I/R.CondusionEsmolol infusion can protect the spinal cord against I/R injury,and inhibition of the expression of HIF-1α is involved in the mechanism.

ObjectiveTo investigate the effect of propofol on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression in thoracic aorta of hypertensive rats.MethodsHealthy SD rats of both sexes weighing 240-280 g were used in this study.Hypertension was induced by subcutaneous deoxycorticosterone 25 mg/kg twice a week for consecutive 7 weeks.Sixty-four hypertensive rats were randomly divided into four groups (n ＝ 16 each):hypertension group (group H),low,medium and high dose propofol group ( groups P1,P2,P3 ).Groups P1,P2 and P3 received infusion of propofol at a rate of 20,30 and 40 mg* kg- 1 · h- 1 for 3 h respectively,while group H received equal volume normal saline instead of propofol.Mean arterial pressure (MAP) was monitored and recorded before,1 h and 3 h after the start of propofol or normal saline infusion.All animals were sacrificed at 3 h of intravenous administration.Blood samples were collected by taking out the eyeballs for determination of serum NO concentrations by nitrate reductase method.The expression of eNOS mRNA,iNOS mBNA was determined by reverse transcription-polymerase chain reaction.The expression of eNOS and iNOS protein was determined by Western blot.ResultsCompared to group H,MAP was decreased significantly,the serum NO concentrations were increased significantly,the expression of eNOS mRNA and protein in thoracic aorta was up-regulated,and the expression of iNOS mRNA and protein in thoracic aorta was down-regulated in a dose-dependent manner in groups P1,P2 and P3 ( P < 0.05 or 0.01 ).ConclusionPropofol can down-regulate iNOS expression and up-regudate eNOS expression in endothelial cells of thoracic aorta and promote NO release in hypertensive rats,Which is the mechanism of propofol decreasing pressure.

Objective To investigate the effect of NR2B antisense oligonucleotide on naloxone-induced withdrawal responses in morphine-dependent rats. Methods Famale SD rats weighing 230-270 g were anesthetized with intraperitoneal pentobarhital 60 mg/kg. Intrathecal (IT)catheter was placed at L3,4 interspace.Thirty-two rats in which FT catheter was successfully placed were randomly divided into 4 groups ( n = 8 each) : group C control; group MD morphine dependence; group AO NR2B antisense oligonucleotide (aNR2B) and group SO NR2B sense oligonucleotide (sNR2B) . In group MD, AO, SO chronic morphine dependence was induced by increasing doses of subcutaneous morphine for 6 days. The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg twice every other day and reached 50 mg/kg on the 6th day. In group AO and SO IT aNR2B or sNR2B 15 nmol was administered simultaneously with subcutaneous morphine. Morphine withdrawal responses was induced by IT naloxone 4 mg/kg and scored based on the responses (0 = normal; higher scores signify severer responses) . The weight loss was calculated.The expression of NR1, NR2A and NR2B mRNA in hippocampus was determined by RT-PCR. Results The morphine withdrawal syndrome and weight loss were significantly incresed in group MD, AO and SO, while NR2B mRNA expression in hippocampus was up-regulated in group MD and SO compared with group C. The morphine withdrawal syndrome and weight loss were significantly decreased, NR2A mRNA expression in hippocampus was up-regulated and NR2B mRNA expression was down-regulated in group AO compared with group MD. There was no significant difference in NR1 mRNA expression between the 4 groups . Conclusion NR2B antisense oligonucleotide can suppress morphine withdrawal responses through the regulation of NMDA receptor level and construction in hippocampus.

Objective To investigate the effects of surgical trauma on synaptic structure in hippocampal CA3 area in aged rats.Methods Fifty-six healthy SD rats aged 18 months were randomly divided into 3 groups: control group (group C, n = 8) , anesthesia group (group A, n = 24) , and operation group (group O, n - 24) . Anesthesia was performed with intraperitoneal ketamine 40 mg/kg but no operation was carried out in group A. Anesthesia was also performed with intraperitoneal ketamine 40 mg/kg, and splenectomy was performed after loss of righting reflex in group O. Eight animals from group A and O selected on 1, 3, and 7 d after anesthesia or operation respectively underwent Morris water maze test for assessment of the cognitive function. The animals were . then decapitated. Hippocampal CA3 area was isolated for examination with electron microscope and the synaptic structure in the polymorphic layer of hippocampal CA3 area was measured. Results Compared to group C and A, the times of passing through the original platform and number of synapses were significantly reduced, the width of synaptic cleft was significantly increased, the thickness of the postsynaptic density was significantly decreased, the length of the active zones was significantly shortened, and the curvature of the synaptic interface and percentage of perforated synapses were significantly decreased at T_(1,2), ( P < 0.05 or 0.01) , but no significant change was found in the indices mentioned above at T_3 in group O(P > 0.05). Compared to group C, the latency and swimming distance were significantly prolonged at T_1 in group A and at T_(1,2) in group O ( P < 0.01) . Compared to group A, the latency at T_(1,2) and the swimming distance at T_2 were significantly prolonged in group O ( P < 0.05) . Conclusion Surgical trauma can induce early postoperative cognitive impairment through changing synaptic structure in hippocampal CA3 area in aged rats.

Objective To compare the impact of propofol and sevoflurane on thermoregulation in children undergoing orheopaedic surgery.Methods Sixty-eight children scheduled to undergo ortho-paedic surgery were randomly allocated to receive propofol (group P)and sevoflurane(group S)anes-thesia,34 cases in each group.Tympanic temperature was recorded 5 minutes before (T0 )and 5 min (T1 ),1 5 min (T2 ),30 min (T3 ),45 min (T4 ),60 min (T5 ),75 min (T6 ),90 min (T7 ),105 min (T8 )and 120 min (T9 )after anesthesia.Total fluid intake,duration of surgery,duration of anesthe-sia,the incidence of hypothermia,and the incidence of shivering were also recorded.Results Com-pared with T0 ,in both groups body temperature declined at T1-T8 .There was no difference between the two groups in total fluid intake,duration of surgery,duration of anesthesia and the incidence of shivering.Compared with group P,children in group S had a higher incidence of hypothermia(8 vs 1). Children in group S had lower temperature,which had statistical significance at T7 and T8 (P <0.05). Conclusion The core temperature of children undergoing orthopaedic surgery showed a trend of in-crease after the first fall in the surgery.Compared with propofol,sevoflurane anesthesia is more likely to lead to the incidence of hypothermia in children undergoing orthopaedic surgery in 90 min after in-duction of anesthesia.

Objective To evaluate the role of spinal c?Jun N?terminal kinase ( JNK ) signaling pathway in incisional pain in rats. Methods Sixty?three adult male Sprague?Dawley rats, weighing 200-250 g, were randomly divided into 3 groups ( n=21 each) using a random number table: incisional pain group ( IP group) , dimethyl sulfoxide ( DMSO) group, and JNK inhibitor SP600125 group ( SP group) . A 1?cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in anesthetized rats. In group DMSO, 10% DMSO 10 μl was injected intrathecally at 30 min before surgery. In group SP, SP600125 25 μg (in 10 μl of 10% DMSO) was injected intrathecally at 30 min before sur?gery. Six rats in each group were sacrificed, and the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before establishment of the model and 2, 6, 24, 48 and 72 h after establishment of the model. After measurement of the pain threshold at 24 h before establishment of the model and 6, 24, 48 and 72 h after establishment of the model, the lumbar segment of the spinal cord was removed for determination of the expression of phosphorylated JNK ( p?JNK) by im?munofluorescence. Results The MWT was significantly lower, the TWL was shorter, and the expression of p?JNK was lower at each time point after establishment of the model than at 24 h before establishment of the model in group IP (P<0?05). Compared with group IP, the MWT was significantly increased, the TWL was prolonged, and the expression of p?JNK was down?regulated at each time point after establishment of the model in group SP ( P<0?05) , and no significant change was found in the parameters mentioned a?bove in group DMSO ( P>0?05) . Conclusion Spinal JNK signaling pathway is involved in the develop?ment and maintenance of incisional pain in rats.

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in attenuation of renal ischemia-reperfusion (I/R) injury by lidocaine pretreatment in rats.Methods Sixty healthy male Wistar rats,weighing 300-350 g,were randomly assigned into 5 groups (n =12 each) using a random number table:sham operation group (group S); renal I/R group (group I/R); lidocaine pretreatment group (group L) ; 5-HD (a specific blocker of the mito-KATP channel) group and 5-HD + lidocaine pretreatment group (group 5-HD + L).Renal ischemia was induced by occlusion of bilateral renal arteries for 60 min with atraumatic microclips followed by 4 h reperfusion.At 60 min before renal ischemia,lidocaine 5 mg/kg was intravenously injected followed by continuous infusion at 2 mg· kg-1 · h-1 in group L.5-HD 10 mg/kg was injected intraperitoneally at 65 min before ischemia in group 5-HD.In 5-HD + L groups,5-HD 10 mg/kg was injected intraperitoneally at 65 min before ischemia and the other procedures were similar to those previously described in group L.In S and I/R groups,the animals received equal volumes of normal saline instead of lidocaine.Blood samples were obtained at 6 h of reperfusion for determination of serum creatinine (Cr) and urea mitrogen (BUN) concentrations.Bilateral kidneys were removed for determination of mitochondrial membrane potential in the renal tubular epidural cells,malondialdehyde (MDA) content,and superoxide dismutase (SOD) activity and for microscopic examination.Results Compared with group S,the serum Cr and BUN concentrations and MDA content were significantly increased,and SOD activity and mitochondrial membrane potential were decreased in I/R,L,5-HD and 5-HD + L groups (P ＜ 0.05).Compared with group I/R,the serum Cr and BUN concentrations and MDA content were significantly decreased,and SOD activity and mitochondrial membrane potential were increased in L and 5-HD + L groups (P ＜ 0.05),and no significant changes were found in the serum Cr and BUN concentrations,MDA content,SOD activity and mitochondrial membrane potential in group 5-HD (P ＞ 0.05).Compared with group L,the serum Cr and BUN concentrations and MDA content were significantly increased,and SOD activity and mitochondrial membrane potential were decreased in 5-HD + L group (P ＜ 0.05).The pathological changes were significantly reduced in group L as compared with I/R and 5-HD + L groups.Conclusion Mito-KATp channels are involved in reduction of I/R-induced renal injury by lidocaine pretreatment in rats.

Objective To investigate the effect of lidocaine pretreatment on renal HMGB1 expression during renal ischemia-reperfusion (I/R) in rats.Methods Thirty-six male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n=12 each):sham operation group (group S),I/R group and lidocaine pretreatment group (group L).Renal I/R was induced by occlusion of bilateral renal arteries for 60 min followed by 4 or 24 h reperfusion.Lidocaine 5 mg/kg was injected iv at 60 min prior to ischemia followed by 2 mg· kg- 1· h- 1 infusion iv for 60 min in group L.Equal volume of normal saline was given in group I/R.Six rats in each group were sacrificed at 4 or 24 h of reperfusionand their kidneys were removed for microscopic examination and for determination of SOD activity,MDA content and the expression of HMGB1 mRNA and protein.Results Compared with group S,renal HMGB1 mRNA and protein expression,MDA content were significantly increased,while SOD activity were significantly decreased in groups I/R and L( P ＜ 0.05).Compared with group I/R,renal HMGB1 mRNA and protein expression,and MDA content were significantly decreased,while SOD activity were significantly increased in group L ( P ＜ 0.05 ).Conclusion Lidocaine pretreatment can attenuate renal I/R injury in rats by down-regulating HMGB1 expression