Objective To investigate the effect of propofol on the expression of c-fos mRNA in hippocampus in rats with visceral pain (VP).Methods Thirty male Sprague-Dawley rats,weighing 180-240 g,were randomly divided into 3 groups (n =10 each):VP group,propofol 7.5 mg/kg group (group P1) and propofol 75.0 mg/kg group (group P2).0.9％ normal saline was injected intravenously via the caudal vein in group VP.Propofol 7.5 and 75.0 mg/kg were injected intravenously via the caudal vein in groups P1 and P2,respectively.VP was produced by colorectal distension in anesthetized rats.The threshold of VP was assessed by the intra-balloon pressure which was limited to 100 mm Hg to avoid damage to intestine before and after administration.The rats were sacrificed after measurement of the pain threshold,their brains were removed and hippocampi were isolated for determination of the expression of c-fos mRNA by RT-PCR.Results Compared with group VP,the threshold of VP was significantly increased and the expression of c-fos mRNA in hippocampus was down-regulated in groups P1 and P2 (P ＜ 0.05).The threshold of VP was significantly higher and the expression of c-fos mRNA in hippocampus was lower in group P2 than in group P1 (P ＜ 0.05).Conclusion Propofol can reduce VP through down-regulating the expression of c-fos mRNA in hippocampus in rats.

Objective To evaluate the role of spinal cord CABAA receptors in the analgesic effect of propofol on visceral pain in rats. Methods Adult female SD rats, weighing 190-240 g, were used in this study.The animals were anesthetized with intraperitoneal ketamine 50-100 mg/kg. Intrathecal (IT) catheters were placed at L5-6 interspace according to the technique described by Storkson et al. Thirty-two animals in which IT catheters were successfully placed were randomly divided into 4 groups ( n = 8 each) : dimethyl sulphoxide (DMSO) group (group D), propofol group (group P), bicuculline group (group B) and bicuculline + propofol group (group B +P). Visceral pain was induced by injecting 10% formalin 100 μl underneath the mucous membrane of rectum.Groups D, P and B received IT DMSO 5 μl, propofol 10 μg and bicuculline 2 μg respectively. Group BP received IT bicuculline 2 μg and then IT propofol 10 μg 10 min later. The L5-S1 segment of the spinal cord was removed 2 h after formalin injection to determine FOS protein expression by hnmuno-histochemistry. Results Compared with groups D and B, FOS protein expression was significantly down-regulated in group P ( P ＜ 0.05 ) . There was no significant difference in FOS protein expression between groups D and B ( P ＞ 0.05) . FOS protein expression was significantly up-regulated in group BP compared with group P ( P ＜ 0.05) . Conclusion Propofol has analgesic effect on visceral pain in rats through spinal cord GABAA receptor action.

Objective To evaluate the effects of dexmedetomidine on the activity of c-Jun N-terminal kinase (JNK) during cerebral ischemia-reperfusion (I/R) in rats.Methods Eighty-one pathogen-free male Sprague-Dawley rats,aged 8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n=27 each) using a random number table:sham operation group (group S);cerebral I/R group (group CI/R);dexmedetomidine group (group Dex).The rats were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.Cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h followed by 24 h of reperfusion in CI/R and Dex groups.The middle cerebral artery was only exposed but not occluded in group S.Dexmedetomidine 3 μg/kg was injected via the tail vein immediately before ischemia followed by infusion at a rate of 3 μg · kg-1 · h-1until 24 h of reperfusion in group Dex,while the equal volume of normal saline was given in S and CI/R groups.The rats were sacrificed at 24 h of reperfusion,and their brains were removed for determination of cerebral infarct size (by TTC staining),brain water content ((wet weight-dry weight)/wet weight × 100％),cell apoptosis (by TUNEL) and expression of phosphorylated JNK (p-JNK) protein (by Western blot analysis).Apoptotic index was calculated.Results Compared with group S,the brain water content,apoptotic index and cerebral infarct size were significantly increased,and the expression of p-JNK was up-regulated in CI/R and Dex groups.Compared with group CI/R,the brain water content,apoptotic index and cerebral infarct size were significantly decreased,and the expression of p-JNK was down-regulated in group Dex.Conclusion Dexmedetomidine reduces cerebral I/R injury through decreasing the activity of JNK and inhibiting cell apoptosis in rats.

Objective To explore the effects and mechanism of propofol on cognitive function of type 2 diabetic rats.Methods Ten of fifty adult male SD rats were fed with basic diet and allocated to control group.Another forty rats were fed with high sugar and high fat for 8 weeks and composite intraperitoneal injection of 1% streptozotocin (STZ)to establish model and then divided into four groups:diabetes group;low dose,middle dose and high dose of propofol group (diabetic rats were given intraperitoneal injection of 1% propofol 10,30,75 mg·kg-1·d-1 for 5 consecutive days).The cognitive functions were examined by Morris water maze from the first day after intraperitoneal injec-tion with propofol.The hippocampus were isolated for observing histopathologic alterations by HE staining and for the determinations of SOD,MDA,CAT,GSH and GSH-PX by colorimetry. Western blot was used to detect the expression of AGEs and RAGE.Results Compared to the control group,there was an obvious increased escape latent period,decreased the frequency of crossing platform,increased hippocampal neurons damage and MDA,decreased levels of SOD, CAT,GSH and GSH-PX,as well as the protein levels of AGEs and RAGE in diabetes group (P <0.05).There was no significant difference between diabetes group and low dose propofol of group on behavior ability and detection index.However,middle dose and high dose of propofol group showed more serious cognitive dysfunction,aggravated hippocampal neurons cells loss,increased oxidative stress as well as enhanced expression of AGEs and RAGE (P <0.05 ).Conclusion Multiple given sedative or anesthetic doses of propofol can aggravate the cognitive dysfunction and oxidative stress in type 2 diabetic rats,which may be related to increase the expression of AGEs and RAGE in brain tis-sue.

Objective To discuss the effects of remifentanfl for delthemte hypotension in intracranial aneurysm clamp operation,evaluating the feasibility and safety.Methods Twenty intracranial aneurysm patients undergoing occlusion surgery were prospectively randomized in to two groups:Group Ⅰ and Group Ⅱ.Group Ⅰ adopted remifentanil for deliberate hypotension and Group Ⅱ adopted sodium nitroprusside.The data were analyzed with SPSS 11.5 for Windows.Results Deliberate hypotension was achieved at the target mean arterial pressure(MAP)for remifentanil and nitroprusside respectively.During deliberate hypotension,HR in Group Ⅰ were lower than that in Group Ⅱ(P<0.01).RPP in Group Ⅰwere lower than that in Group Ⅱ(P<0.01).Blood loss in Group Ⅰ were lower than that in Group Ⅱ(P<0.05).Conclusion For general anesthesia in intracranial aneurysm clamp operation,using remifentanil for deliberate hypotemion is a good choice.

Objective To investigate the role of spinal cord opioid receptors in the antinocieeptive effect of propefol in rats. Methods Male SD rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. Intratbecal (IT) catheter was placed at L5～6 interspace. Correct placement was confirmed by lower extremity motor block after injection of 2% lidocaine 15 μl via the iv catheter. Animals which were lame or paralyzed were excluded. Ninety SD rats in which IT catheters were successfully placed were randomly divided into 9 groups (n = 10 each): group Ⅰ propofol 10μg IT (P);group Ⅱ dimethyl suipbexide (DMSO-solvent for propofol) 5 μl IT (D);group Ⅲ artificial cerebral spinal fluid (ACSF) 5 μl IT;group Ⅳ propoful 10 μl + naloxone 15 μg IT (PN);group Ⅴ DMSO 5 μl IT + naloxone 15 μg IT (DN);group Ⅳ propofol 10μg IT + CTOP Ⅰμg IT (PC);group Ⅶ DMSO 5 μl IT + CTOP 1μg IT (DC);group Ⅷ propofol 10 μg IT + ICI 174, 864 1 μg IT (PI) and group ⅨDMSO 5 μl 1T + ICI 174, 864 1 μg IT (DI). In group Ⅳ-Ⅸ naloxone or CTOP (μ-receptor antagonist) or ICI 174, 864 (δ-receptor antagonist) was injected 5 min after propofol/DMSO. Pain threshold was measured before the first drug administration (T0) and at 10 min (T1), 20 min (T2) and 40 min (T3) after the first drug administration using hot water tail-withdrawal test. The latency for withdrawal of the tail from hot water was recorded. Results The pain threshold was significantly higher in group P, PN, PC and PI than in group D, DN, DC and DI respectively. The pain threshold was significantly increased at T1.2 compared with the baseline value at T0 in group P, PN, PC and PI. The pain threshold was significantly lower at T3 than at T1 and T2 in group P, PN, PC and PI. The pain threshold was significantly lower after drug administration in group PN and PI than in group P and PC. Conclusion Spinal cord δ-oploid receptors are involved in the anfinocicepfive effect of propofol.

Objective To investigate the effects of surgical trauma on Toll?like receptor 4 ( TLR4) expression in the hippocampus of aged mice. Methods Ninety male Kunming mice, aged 16-18 months, weighing 30-40 g, were randomly divided into 3 groups ( n=30 each) using a random number table:control group ( group C), anesthesia group ( group A), and partial hepatectomy group ( group PH). Normal saline 0.1 ml∕10 g was injected intraperitoneally in group C. In group A, fentanyl 0.2 mg∕kg and droperidol 5 mg∕kg were injected intraperitoneally. In group PH, fentanyl 0. 2 mg∕kg and droperidol 5 mg∕kg were injected intraperitoneally, and the mice underwent partial hepatectomy. Cognitive function was assessed using Morris water maze test at 1, 3, and 7 days after anesthesia or surgery. After the end of the test, the hippocampus was immediately harvested for determination of the TLR4, tumor necrosis factor?alpha ( TNF?α) and interleukin?1 beta ( IL?1β) protein and mRNA expression by Western blot and real?time reverse transcriptase?polymerase chain reaction, respectively. Results Compared with group C, no significant changes were found in group PH in the escape latency, percentage of swimming distance in the target quadrant, and TLR4, TNF?α and IL?1β protein and mRNA expression at each time point after anesthesia in group A (P>0.05), and the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF?α and IL?1βprotein and mRNA was up?regulated at 1 and 3 days after surgery in group PH ( P<0. 05 or 0. 01 ) . Compared with group A, the escape latency was significantly prolonged, the percentage of swimming distance in the target quadrant was decreased, and the expression of TLR4, TNF?αand IL?1βprotein and mRNA was up?regulated at 1 and 3 days after surgery in group PH (P<0.05 or 0.01). Conclusion Surgical trauma can up?regulate the expression of TLR4 in the hippocampus of aged mice, which may be involved in the mechanism of surgical trauma?induced postoperative cognitive dysfunction.

Objective To investigate the effect of postoperative analgesia with difference methods on immunity in patients after thoracic tumour surgery. Methods Forty ASA Ⅰ-Ⅱ patients aged 35-65 years old undergoing thoracic tumour surgery were randomized to receive either postoperative patient- controlled intravenous analgesia (PCIA) (group Ⅰ, 20 cases) or patient-controlled epidural analgesia (PCEA) (group E, 20 cases) for 48 h. Medicine compatibility in group Ⅰ: sulfentanyl 1μg/ml, tropisetron 0.05 mg/ml, the PCIA pump was set up to deliver a 5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h. Epidual catheter was placed at T4-5interspace before induction of anesthesia in group E. The PCEA solution contained 2 mg/ml ropivacaine. The PCEA pump was set up to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h after a loading dose of 0.33% ropivacame 6 ml. The VAS score, Ramsay sedation score and complications were reeorded. Blood samples were taken before induction (baseline) and at 2 h and 1st, 3rd and 7th day after surgery for determination of plasma concentrations of cortisol, interleukin 2 (IL-2) and the level of natural killer (NK) cells and eytokine-induced killer (CIK) cells. Results There was no significant difference in VAS score at 2 h after operation between two groups [(1.8±0.3) scores in group Ⅰ and (1.8±0.5)scores in group E].Ramsay sedation score at Ist, 3rd and 7th day after operation in group E were significantly lower than those in group Ⅰ (P<0.05), The plasma concentration of cortisol at 2 h and Ist, 3rd, 7th day after operation in group Ewere significantly lower than those in group Ⅰ (P<0.05), the levels of IL-2, NK cells and CIK cells in group E were significantly higher than those in group Ⅰ (P<0.05). Conclusions The efficacy of postoperative PCEA in improving immunity after thoracic tumour surgery is better than that of postoperative PCIA.

Objective To determine the median effective dose (ED50) of hemocoagulase agkistrodon (HCA) inhibiting the bleeding after trans-bronchial lung biopsy (TBLB).Methods ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 45-75 yr,body mass index 19-24 kg/m2,scheduled for elective TBLB,were enrolled in this study.TBLB was performed after routine anesthesia.HCA diluted in normal saline 5 ml was locally injected into the biopsy site at 2 min before surgery.The initial dose of HCA was 1.4 U.The dose of HCA was determined by up and down sequential method.Each time the dose of HCA increased/decreased in the next patient depending on whether nor not the bleeding was observed in the biopsy wound under fiberoptic bronchoscope.The ratio between the two successive concentrations was 1.2.The ED50 and 95 ％ confidence interval of HCA were calculated by Dixon's up-and-down method.Results ED50 of HCA inhibiting the bleeding after TBLB was 0.9 U,and 95 ％ confidence interval was 0.7-1.1 U.Conclusion ED50 of HCA inhibiting the bleeding after TBLB is 0.9 U.

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATe) channels in attenuation of cerebral ischemia-reperfusion (I/R) injury by dexmedetomidine in rats.Methods One hundred and twenty healthy male Wistar rats,weighing 290-340 g,were randomly assigned into 5 groups (n =24 each) using a random number table:sham operation group (group S) ; group I/R; dexmedetomidine group (group D) ; 5-HD (a specific blocker of mito-KATPchannel) group and 5-HD + dexmedetomidine group (group 5-HD + D).The rats were anesthetized with intraperitoneal chloral hydrate.Focal cerebral I/R was produced by 2 h middle cerebral artery occlusion followed by reperfusion.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally before ischemia and after onset of reperfusion.In group 5-HD,5-HD 30 mg/kg was injected intraperitoneally at 1 h before ischemia.In 5-HD + D group,5-HD 30 mg/kg was injected intraperitoneally at 1 h before ischemia and the other procedures were similar to those previously described in group D.Twelve rats were chosen at 24 and 48 h of reperfusion to assess the neurological deficit score (NDS).The animals were then sacrificed and brains were removed for determination of cerebral infarct size by TTC staining.Results Compared with S group,NDS and cerebral infarct size were significantly increased at each time point in the other four groups (P ＜ 0.05).Compared with group I/R,NDS and cerebral infarct size were significantly decreased in D and 5-HD + D groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in 5-HD group (P ＞ 0.05).Compared with group D,NDS and infarct size were significantly increased in group 5-HD + D (P ＜ 0.05).Conclusion Mito-KATP channels are involved in reduction of I/R-induced cerebral injury by dexmedetomidine in rats.